AIM： To identify the gene （s） related to the antagonistic activity of Enterobacter cloacae B8 and to elucidate its antagonistic mechanism. METHODS： Transposon-mediated mutagenesis and tagging method and cassette P...AIM： To identify the gene （s） related to the antagonistic activity of Enterobacter cloacae B8 and to elucidate its antagonistic mechanism. METHODS： Transposon-mediated mutagenesis and tagging method and cassette PCR-based chromosomal walking method were adopted to isolate the mutant strain （s） of B8 that lost the antagonistic activity and to clone DNA fragments around Tn5 insertion site. Sequence compiling and open reading frame （ORF） finding were done with DNAStar program and homologous sequence and conserved domain searches were performed with BlastN or BlastP programs at www.ncbi.nlm.nih.gov. To verify the gene involved in the antagonistic activity, complementation of a full-length clone of the anrFgene to the mutant B8F strain was used. RESULTS： A 3 321 bp contig around the Tn5 insertion site was obtained and an ORF of 2 634 bp in length designated as anrFgene encoding for a 877 aa polyketide synthase-like protein was identified. It had a homology of 83% at the nucleotide level and 79% ID/87% SIM at the protein level, to the admM gene of Pantoea agglomerans andrimid biosynthetic gene cluster （AY192157）. The Tn5 was inserted at 2 420 bp of the gene corresponding to the COG3319 （the thioesterase domain of type I polyketide synthase） coding region on BSF. The antagonistic activity against Xanthomonas oryzae pv. oryzae was resumed with complementation of the full-length anrFgene to the mutant B8F. CONCLUSION： The anrFgene obtained is related to the antagonistic activity of BS, and the antagonistic substances produced by B8 are andrimid and/or its analogs.展开更多
The present study was designed to identify the difference between two rapamycin biosynthetic gene clusters from Streptomyces hygroscopicus ATCC29253 and Actinoplanes sp. N902-109 by comparing the sequence and organiza...The present study was designed to identify the difference between two rapamycin biosynthetic gene clusters from Streptomyces hygroscopicus ATCC29253 and Actinoplanes sp. N902-109 by comparing the sequence and organization of the gene clusters. The biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus ATCC29253 was reported in 1995. The second rapamycin producer, Actinoplanes sp. N902-109, which was isolated in 1995, could produce more rapamycin than Streptomyces hygroscopicus ATCC29253. The genomic map of Actinoplanes sp. N902-109 has been elucidated in our laboratory. Two gene clusters were compared using the online software anti-SMASH, Glimmer 3.02 and Subsystem Technology(RAST). Comparative analysis revealed that the organization of the multifunctional polyketide synthases(PKS) genes: Rap A, RapB, RapC, and NRPS-like RapP were identical in the two clusters. The genes responsible for precursor synthesis and macrolactone modification flanked the PKS core region in N902-109, while the homologs of those genes located downstream of the PKS core region in ATCC29253. Besides, no homolog of the gene encoding a putative type II thioesterase that may serve as a PKS "editing" enzyme accounted for over-production of rapamycin in N902-109, was found in ATCC29253. Furthermore, no homologs of genes rapQ(encoding a methyltransferase) and rap G in N902-109 were found in ATCC29253, however, an extra rap M gene encoding methyltransferase was discovered in ATCC29253. Two rapamycin biosynthetic gene clusters displayed overall high homology as well as some differences in gene organization and functions.展开更多
The extreme environment of the polar regions has driven the evolution of unique metabolic mechanisms in microorganisms,resulting in structurally diverse and highly active secondary metabolites.These metabolites are no...The extreme environment of the polar regions has driven the evolution of unique metabolic mechanisms in microorganisms,resulting in structurally diverse and highly active secondary metabolites.These metabolites are not only crucial for microbial adaptation to extreme conditions,but also exhibit significant potential for applications in medicine,agriculture(e.g.,biocontrol),and industry.This review provides a comprehensive overview of 111 secondary metabolites derived from polar microorganisms reported between 2013 and 2025,with a focus on advances in their classification,biological activities,and biosynthetic gene cluster mining techniques.Additionally,it highlights key strategies for advancing future investigations,providing a valuable reference for continued exploration in this promising field.Notably,polar microbial secondary metabolites also hold promising applications in agriculture,particularly in biocontrol,soil health enhancement,and stress-resistant crop development.展开更多
Dear Editor,Saponins are one of the most abundant and diverse groups of natural plant products,playing critical roles in plant defense against disease and herbivores,and some saponins have gained recognition for their...Dear Editor,Saponins are one of the most abundant and diverse groups of natural plant products,playing critical roles in plant defense against disease and herbivores,and some saponins have gained recognition for their pharmaceutical importance.Saponins are glycosides of triterpenes,with their triterpene backbones formed through the cyclization of the 2,3-oxidosqualene by oxidosqualene cyclase(OsC).The triterpenes are oxidized mostly by cytochrome P450(CYP450)and glycosylated by uridine diphosphate(UDP)-glycosyltransferases(UGTs)or cellulose synthase-like enzymes(CSLs)to form diverse saponins(Abe et al.,2004;Seki et al.,2015).展开更多
Teucrium chamaedrys,commonly known as wall germander,is a small woody shrub native to the Mediterranean region.Its name is derived from the Greek words meaning‘‘ground oak,’’as its tiny leaves resemble those of an...Teucrium chamaedrys,commonly known as wall germander,is a small woody shrub native to the Mediterranean region.Its name is derived from the Greek words meaning‘‘ground oak,’’as its tiny leaves resemble those of an oak tree.Teucrium species are prolific producers of diterpenes,endowing them with valuable properties widely utilized in traditional and modern medicine.Sequencing and assembly of the 3-Gbp tetraploid T.chamaedrys genome revealed 74 diterpene synthase genes,with a substantial number of these genes clustered at four synteny genomic loci,each harboring a copy of a large diterpene biosynthetic gene cluster.Comparative genomics revealed that this cluster is conserved in the closely related species Teucrium marum.Along with the presence of several cytochrome p450 sequences,this region is among the largest biosynthetic gene clusters identified.Teucrium is well known for accumulating clerodane-type diterpenoids,which are produced from a kolavenyl diphosphate precursor.To elucidate the complex biosynthetic pathways of these medicinal compounds,we identified and functionally characterized several kolavenyl diphosphate synthases from T.chamaedrys.The remarkable chemical diversity and tetraploid nature of T.chamaedrys make it a valuable model for studying genomic evolution and adaptation in plants.展开更多
Northern wild rice(NWR;Zizania palustris L.),an annual aquatic plant in the Poaceae family,has high economic importance due to its nutrient-rich grains.However,the existing NWR genome assembly for this species has sev...Northern wild rice(NWR;Zizania palustris L.),an annual aquatic plant in the Poaceae family,has high economic importance due to its nutrient-rich grains.However,the existing NWR genome assembly for this species has severe fragmentation and incomplete gene representation.A near-complete genome was assembled in this study to provide a high-quality genomic reference for NWR-associated research.The assembled genome exhibited a total contig length of 1.41 Gb and a contig N50 of 109.22 Mb.Overall,a 73.60%repetitive sequence content was identified and 47,804 genes predicted.Phylogenetic analysis indicated that Z.palustris was most closely related to Zizania latifolia,with an estimated divergence time of 4.57–8.15 Mya.Meanwhile,Z.palustris underwent a recent,species-specific long terminal repeat(LTR)expansion,associated with its larger genome size.We identified two genomic blocks in the Z.palustris and Z.latifolia genomes that exhibit strong synteny with the rice phytocassane biosynthetic gene cluster.The centromeric satellite repeats in Z.palustris identified in this study primarily comprised a 145 bp repetitive unit.The findings also revealed centromere homogenisation and rearrangement accompanied by LTR invasion in NWR.Among the genes missing in the previous NWR genome,we observed LTR insertion events that resulted in expanded gene lengths in our updated NWR genome.The present updated NWR genome provides a valuable resource for crop genetic improvement,functional gene discovery,and research on critical biological processes.展开更多
Benzoxazinoids are a class of protective and allelopathic plant secondary metabolites that have been identified in multiple grass species and are encoded by the Bx biosynthetic gene cluster(BGC)in maize.Data mining of...Benzoxazinoids are a class of protective and allelopathic plant secondary metabolites that have been identified in multiple grass species and are encoded by the Bx biosynthetic gene cluster(BGC)in maize.Data mining of 41 high-quality grass genomes identified complete Bx clusters(containing genes Bx1–Bx5 and Bx8)in three genera(Zea,Echinochloa,and Dichanthelium)of Panicoideae and partial clusters in Triticeae.The Bx cluster probably originated from gene duplication and chromosomal translocation of native homologs of Bx genes.An ancient Bx cluster that included additional Bx genes(e.g.,Bx6)is presumed to have been present in ancestral Panicoideae.The ancient Bx cluster was putatively gained by the Triticeae ancestor via horizontal transfer(HT)from the ancestral Panicoideae and later separated into multiple segments on different chromosomes.Bx6 appears to have been under less constrained selection compared with the Bx cluster during the evolution of Panicoideae,as evidenced by the fact that it was translocated away from the Bx cluster in Zea mays,moved to other chromosomes in Echinochloa,and even lost in Dichanthelium.Further investigations indicate that purifying selection and polyploidization have shaped the evolutionary trajectory of Bx clusters in the grass family.This study provides the first candidate case of HT of a BGC between plants and sheds new light on the evolution of BGCs.展开更多
Methylobacterium species,the representative bacteria distributed in phyllosphere region of plants,often synthesize carotenoids to resist harmful UV radiations.Methylobacterium extorquens is known to produce a caroteno...Methylobacterium species,the representative bacteria distributed in phyllosphere region of plants,often synthesize carotenoids to resist harmful UV radiations.Methylobacterium extorquens is known to produce a carotenoid pigment and recent research revealed that this carotenoid has a C_(30) backbone.However,its exact structure remains unknown.In the present study,the carotenoid produced by M.extorquens AM1 was isolated and its structure was determined as 4-[2-O-11Z-octadecenoyl-β-glucopyranosyl]-4,4′-diapolycopenedioc acid(1),a glycosylated C_(30) carotenoid.Furthermore,the genes related to the C_(30)carotenoid synthesis were investigated.Squalene,the precursor of the C_(30) carotenoid,is synthesized by the co-occurrence of META1p1815,META1p1816 and META1p1817.Further overexpression of the genes related to squalene synthesis improved the titer of carotenoid 1.By using gene deletion and gene complementation experiments,the glycosyltransferase META1p3663 and acyltransferase META1p3664 were firstly confirmed to catalyze the tailoring steps from 4,4′-diapolycopene-4,4′-dioic acid to carotenoid 1.In conclusion,the structure and biosynthetic genes of carotenoid 1 produced by M.extorquens AM1 were firstly characterized in this work,which shed lights on engineering M.extorquens AM1 for producing carotenoid 1 in high yield.展开更多
A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which ...A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.展开更多
Plants and microbes are closely associated with each other in their ecological niches.Much has been studied about plant-microbe interactions,but little is known about the effect of phytochemicals on microbes at the mo...Plants and microbes are closely associated with each other in their ecological niches.Much has been studied about plant-microbe interactions,but little is known about the effect of phytochemicals on microbes at the molecular level.To access the products of cryptic biosynthetic gene clusters in bacteria,we incorporated an organic extract of hibiscus flowers into the culture media of different Actinobacteria isolated from plant rhizospheres.This approach led to the production of broad-spectrum dithiolopyrrolone(DTP)antibiotics,thiolutin(1)and aureothricin(2),by Streptomyces sp.MBN2-2.The compounds from the hibiscus extract responsible for triggering the production of these two DTPs were found to be hibiscus acid dimethyl ester(3)and hydroxycitric acid 1,3-dimethyl ester(4).It was subsequently found that the addition of either Fe2+or Fe3+to culture media induced the production of 1 and 2.The Chrome Azurol S(CAS)assay revealed that 3 and 4 can chelate iron,and therefore,the mechanism leading to the production of thiolutin and aureothricin appears to be related to changes in iron concentration levels.This work supports the idea that phytochemicals can be used to activate the production of cryptic microbial biosynthetic gene clusters and further understand plant-microbe interactions.展开更多
Genome mining has revealed that Penicillium spp.possess numerous down-regulated or cryptic biosynthetic gene clusters(BGCs).This finding hinted that our investigation of fungal secondary metabolomes is limited.Herein,...Genome mining has revealed that Penicillium spp.possess numerous down-regulated or cryptic biosynthetic gene clusters(BGCs).This finding hinted that our investigation of fungal secondary metabolomes is limited.Herein,we report a genetically-modified activation strategy to characterize the spectrum of sesquiterpenoids produced by Penicillium brasilianum CGMCC 3.4402.The cryptic or down-regulated pathways were stimulated by constitutive expression of pathway-specific regulator gene berA responsible for berkeleyacetals biosynthesis from Neosartorya glabra.Chemical analysis of the extracts from the mutant strain Pb-OE:berA enabled the isolation of two new compounds including one bisabolene-type arpenibisabolane C(1),one daucane-type arpenicarotane C(4),along with four known sesquiterpenoids including arpenibisabolane A(2),eupenicisirenins A(3),arpenicarotane B(5)and aspterric acid(6).The assignments of their structures were elucidated from detailed analyses of spectroscopic data,electronic circular dichroism calculation,and biogenetic considerations.The bioassay of isolated compounds(1-6)exhibited no cytotoxic activities against three tumor cells including MCF-7,HepG2,and A549.Arpenibisabolane C(1)and A(2)showed weak inhibition bioactivities on aquatic pathogens Vibrio owensii and Vibrio algivorus.Moreover,phylogenetic analysis and sequence alignments of crucial sesquiterpene synthases were performed.Based on the chemical structures and biogenetic investigations,a hypothetic pathway of new compounds(1,4)was proposed.展开更多
Bacteria living in sediments play essential roles in marine ecosystems and deeper insights into the ecology and biogeochemistry of these largely unexplored organisms can be obtained from‘omics’approaches.Here,we cha...Bacteria living in sediments play essential roles in marine ecosystems and deeper insights into the ecology and biogeochemistry of these largely unexplored organisms can be obtained from‘omics’approaches.Here,we characterized metagenome-assembled-genomes(MAGs)from the surface sediment microbes of the Venice Lagoon(northern Adriatic Sea)in distinct sub-basins exposed to various natural and anthropogenic pressures.MAGs were explored for biodiversity,major marine metabolic processes,anthropogenic activity-related functions,adaptations at the microscale,and biosynthetic gene clusters.Starting from 126 MAGs,a non-redundant dataset of 58 was compiled,the majority of which(35)belonged to(Alpha-and Gamma-)Proteobacteria.Within the broad microbial metabolic repertoire(including C,N,and S metabolisms)the potential to live without oxygen emerged as one of the most important features.Mixotrophy was also found as a successful lifestyle.Cluster analysis showed that different MAGs encoded the same metabolic patterns(e.g.,C fixation,sulfate oxidation)thus suggesting metabolic redundancy.Antibiotic and toxic compounds resistance genes were coupled,a condition that could promote the spreading of these genetic traits.MAGs showed a high biosynthetic potential related to antimicrobial and biotechnological classes and to organism defense and interactions as well as adaptive strategies for micronutrient uptake and cellular detoxification.Our results highlighted that bacteria living in an impacted environment,such as the surface sediments of the Venice Lagoon,may benefit from metabolic plasticity as well as from the synthesis of a wide array of secondary metabolites,promoting ecosystem resilience and stability toward environmental pressures.展开更多
Biosynthetic gene clusters(BGCs)are regions of a genome where genes involved in a biosynthetic pathway are in proximity.The origin and evolution of plant BGCs as well as their role in specialized metabolism remain lar...Biosynthetic gene clusters(BGCs)are regions of a genome where genes involved in a biosynthetic pathway are in proximity.The origin and evolution of plant BGCs as well as their role in specialized metabolism remain largely unclear.In this study,we have assembled a chromosome-scale genome of Japanese catnip(Schizonepeta tenuifolia)and discovered a BGC that contains multiple copies of genes involved in four adjacent steps in the biosynthesis of p-menthane monoterpenoids.This BGC has an unprecedented bipartite structure,with mirrored biosynthetic regions separated by 260 kilobases.This bipartite BGC includes identical copies of a gene encoding an old yellow enzyme,a type of flavin-dependent reductase.In vitro assays and virus-induced gene silencing revealed that this gene encodes the missing isopiperitenone reductase.This enzyme evolved from a completely different enzyme family to isopiperitenone reductase from closely related Mentha spp.,indicating convergent evolution of this pathway step.Phylogenomic analysis revealed that this bipartite BGC has emerged uniquely in the S.tenuifolia lineage and through insertion of pathway genes into a region rich in monoterpene synthases.The cluster gained its bipartite structure via an inverted duplication.The discovered bipartite BGC for p-menthane biosynthesis in S.tenuifolia has similarities to the recently described duplicated p-menthane biosynthesis gene pairs in the Mentha longifolia genome,providing an example of the convergent evolution of gene order.This work expands our understanding of plant BGCs with respect to both form and evolution,and highlights the power of BGCs for gene discovery in plant biosynthetic pathways.展开更多
In silico methods for linking genomic space to chemical space have played a crucial role in genomics driven discovery of new natural products as well as biosynthesis of altered natural products by engineering of biosy...In silico methods for linking genomic space to chemical space have played a crucial role in genomics driven discovery of new natural products as well as biosynthesis of altered natural products by engineering of biosynthetic pathways.Here we give an overview of available computational tools and then briefly describe a novel computational framework,namely retro-biosynthetic enumeration of biosynthetic reactions,which can add to the repertoire of computational tools available for connecting natural products to their biosynthetic gene clusters.Most of the currently available bioinformatics tools for analysis of secondary metabolite biosynthetic gene clusters utilize the“Genes to Metabolites”approach.In contrast to the“Genes to Metabolites”approach,the“Metabolites to Genes”or retro-biosynthetic approach would involve enumerating the various biochemical transformations or enzymatic reactions which would generate the given chemical moiety starting from a set of precursor molecules and identifying enzymatic domains which can potentially catalyze the enumerated biochemical transformations.In this article,we first give a brief overview of the presently available in silico tools and approaches for analysis of secondary metabolite biosynthetic pathways.We also discuss our preliminary work on development of algorithms for retro-biosynthetic enumeration of biochemical transformations to formulate a novel computational method for identifying genes associated with biosynthesis of a given polyketide or nonribosomal peptide.展开更多
Tunicamycin,a potent reversible translocase I inhibitor,is produced by several Actinomycetes species.The tunicamycin structure is highly unusual,and contains an 11-carbon dialdose sugar and anα,β-1″,11′-glycosidic...Tunicamycin,a potent reversible translocase I inhibitor,is produced by several Actinomycetes species.The tunicamycin structure is highly unusual,and contains an 11-carbon dialdose sugar and anα,β-1″,11′-glycosidic linkage.Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression(HHE)strategy combined with a bioassay.Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains,demonstrating the role of the genes for the biosynthesis of tunicamycins.Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes(tunA–tunL).Amongst these is a putative radical SAM enzyme(Tun B)with a potentially unique role in biosynthetic carbon-carbon bond formation.Hence,a seven-step novel pathway is proposed for tunicamycin biosynthesis.Moreover,two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827.These data provide clarification of the novel mechanisms for tunicamycin biosynthesis,and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.展开更多
Natural products(NPs)afforded by living-beings,especially by microscopic species,represent invaluable and indispensable reservoirs for drug leads in clinical practice.With the rapid advancement in sequencing technolog...Natural products(NPs)afforded by living-beings,especially by microscopic species,represent invaluable and indispensable reservoirs for drug leads in clinical practice.With the rapid advancement in sequencing technology and bioinformatics,the ever-increasing number of microbial biosynthetic gene clusters(BGCs)were decrypted,while a great deal of BGCs remain cryptic or inactive under standard laboratory culture conditions.Addressing this dilemma requires innovative tactics to awaken quiescence of BGCs by releasing the potential of microbial secondary metabolism for mining novel NPs.In this study,a universal strategy was proposed to induce the expression of silent BGCs by leveraging the dynamic interactions among coexisting microbial neighbors within a microbiota.This approach involves the deconstruction/reconstruction of binary interactions among the coex-isting neighbors to create a pipeline for BGCs arousing.Coupled with the acquisition of 2760 microbial in-dividuals from the Apocynum venetum(Luobuma,LBM)phyllosphere in a successive dilution procedure,44 culturable isolates were screened using binary interaction,in which 12.6%pairs demonstrated potent mutual interacting effects.Furthermore,after selecting the four most promising isolates,a full-scale metabolic inspection was conducted,in which 25.3%of the interacting pairs showcased significant metabolomic variations with de-cryptic activities.Notably,with the aid of visualization of IMS technology,one of the physiologically functional entities,the bactericidal agent resistomycin,was elucidated from the core interacting pair between the co-culture of the Streptomyces sp.LBM_605 and the Rhodococcus sp.LBM_791.This study highlights the intrinsic interactions among coexisting microorganisms within a phyllosphere microbiota as novel avenues for exploring and har-nessing NPs.展开更多
Plants produce a remarkable diversity of structurally and functionally diverse natural chemicals that serve as adaptive compounds throughout their life cycles.However,unlocking this metabolic diversity is significantl...Plants produce a remarkable diversity of structurally and functionally diverse natural chemicals that serve as adaptive compounds throughout their life cycles.However,unlocking this metabolic diversity is significantly impeded by the size,complexity,and abundant repetitive elements of typical plant genomes.As genome sequencing becomes routine,we anticipate that links between metabolic diversity and genetic variation will be strengthened.In addition,an ever-increasing number of plant genomes have revealed that biosynthetic gene clusters are not only a hallmark of microbes and fungi;gene clusters for various classes of compounds have also been found in plants,and many are associated with important agronomic traits.We present recent examples of plant metabolic diversification that have been discovered through the exploration and exploitation of various genomic and pan-genomic data.We also draw attention to the fundamental genomic and pan-genomic basis of plant chemodiversity and discuss challenges and future perspectives for investigating metabolic diversity in the coming pan-genomics era.展开更多
The genomic era has revolutionized research on secondary metabolites and bioinformatics methods have in recent years revived the antibiotic discovery process after decades with only few new active molecules being iden...The genomic era has revolutionized research on secondary metabolites and bioinformatics methods have in recent years revived the antibiotic discovery process after decades with only few new active molecules being identified.New computational tools are driven by genomics and metabolomics analysis,and enables rapid identification of novel secondary metabolites.To translate this increased discovery rate into industrial exploitation,it is necessary to integrate secondary metabolite pathways in the metabolic engineering process.In this review,we will describe the novel advances in discovery of secondary metabolites produced by filamentous fungi,highlight the utilization of genome-scale metabolic models(GEMs)in the design of fungal cell factories for the production of secondary metabolites and review strategies for optimizing secondary metabolite production through the construction of high yielding platform cell factories.展开更多
Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(AR...Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.展开更多
Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compo...Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compounds with high yields.This review summarized the commonly used regulatory strategies for natural products discovery and overproduction in Streptomyces from three main aspects,including regulator-related strategies,promoter engineering,as well as other strategies employing transposons,signal factors,or feedback regulations.It is expected that the metabolic regulation network of Streptomyces will be elucidated more comprehensively to shed light on natural products research in the future.展开更多
基金Supported by the National Natural Science Foundation of China,No. 39870034the National High Technology Research and Development Program of China, the 863 Program, No. 104-04-01-01the Major Project of Science and Technology Development of Zhejiang Province, No. 021102529
文摘AIM： To identify the gene （s） related to the antagonistic activity of Enterobacter cloacae B8 and to elucidate its antagonistic mechanism. METHODS： Transposon-mediated mutagenesis and tagging method and cassette PCR-based chromosomal walking method were adopted to isolate the mutant strain （s） of B8 that lost the antagonistic activity and to clone DNA fragments around Tn5 insertion site. Sequence compiling and open reading frame （ORF） finding were done with DNAStar program and homologous sequence and conserved domain searches were performed with BlastN or BlastP programs at www.ncbi.nlm.nih.gov. To verify the gene involved in the antagonistic activity, complementation of a full-length clone of the anrFgene to the mutant B8F strain was used. RESULTS： A 3 321 bp contig around the Tn5 insertion site was obtained and an ORF of 2 634 bp in length designated as anrFgene encoding for a 877 aa polyketide synthase-like protein was identified. It had a homology of 83% at the nucleotide level and 79% ID/87% SIM at the protein level, to the admM gene of Pantoea agglomerans andrimid biosynthetic gene cluster （AY192157）. The Tn5 was inserted at 2 420 bp of the gene corresponding to the COG3319 （the thioesterase domain of type I polyketide synthase） coding region on BSF. The antagonistic activity against Xanthomonas oryzae pv. oryzae was resumed with complementation of the full-length anrFgene to the mutant B8F. CONCLUSION： The anrFgene obtained is related to the antagonistic activity of BS, and the antagonistic substances produced by B8 are andrimid and/or its analogs.
基金supported by the National Major Scientific Instruments and Equipment Development Projects(No.2011YQ15007208)Shanghai Science and Technology Support Project(No.12431901102)
文摘The present study was designed to identify the difference between two rapamycin biosynthetic gene clusters from Streptomyces hygroscopicus ATCC29253 and Actinoplanes sp. N902-109 by comparing the sequence and organization of the gene clusters. The biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus ATCC29253 was reported in 1995. The second rapamycin producer, Actinoplanes sp. N902-109, which was isolated in 1995, could produce more rapamycin than Streptomyces hygroscopicus ATCC29253. The genomic map of Actinoplanes sp. N902-109 has been elucidated in our laboratory. Two gene clusters were compared using the online software anti-SMASH, Glimmer 3.02 and Subsystem Technology(RAST). Comparative analysis revealed that the organization of the multifunctional polyketide synthases(PKS) genes: Rap A, RapB, RapC, and NRPS-like RapP were identical in the two clusters. The genes responsible for precursor synthesis and macrolactone modification flanked the PKS core region in N902-109, while the homologs of those genes located downstream of the PKS core region in ATCC29253. Besides, no homolog of the gene encoding a putative type II thioesterase that may serve as a PKS "editing" enzyme accounted for over-production of rapamycin in N902-109, was found in ATCC29253. Furthermore, no homologs of genes rapQ(encoding a methyltransferase) and rap G in N902-109 were found in ATCC29253, however, an extra rap M gene encoding methyltransferase was discovered in ATCC29253. Two rapamycin biosynthetic gene clusters displayed overall high homology as well as some differences in gene organization and functions.
基金supported by National Natural Science Foundation of China(Grant nos.32130109,41761134050).
文摘The extreme environment of the polar regions has driven the evolution of unique metabolic mechanisms in microorganisms,resulting in structurally diverse and highly active secondary metabolites.These metabolites are not only crucial for microbial adaptation to extreme conditions,but also exhibit significant potential for applications in medicine,agriculture(e.g.,biocontrol),and industry.This review provides a comprehensive overview of 111 secondary metabolites derived from polar microorganisms reported between 2013 and 2025,with a focus on advances in their classification,biological activities,and biosynthetic gene cluster mining techniques.Additionally,it highlights key strategies for advancing future investigations,providing a valuable reference for continued exploration in this promising field.Notably,polar microbial secondary metabolites also hold promising applications in agriculture,particularly in biocontrol,soil health enhancement,and stress-resistant crop development.
基金supported by the Key Area Research and Development Program of Guangdong Province(2022B0202070003)supported by the National Science Foundation of China(32072547 and 32372665).
文摘Dear Editor,Saponins are one of the most abundant and diverse groups of natural plant products,playing critical roles in plant defense against disease and herbivores,and some saponins have gained recognition for their pharmaceutical importance.Saponins are glycosides of triterpenes,with their triterpene backbones formed through the cyclization of the 2,3-oxidosqualene by oxidosqualene cyclase(OsC).The triterpenes are oxidized mostly by cytochrome P450(CYP450)and glycosylated by uridine diphosphate(UDP)-glycosyltransferases(UGTs)or cellulose synthase-like enzymes(CSLs)to form diverse saponins(Abe et al.,2004;Seki et al.,2015).
基金support of the Neogen Land Grant Prize,an endowed grant program administered by the Office of Research and Innovation at Michigan State University(MSU),which supports graduate students in translating their research into real-world applications that positively impact society and the US economyfunded by a National Science Foundation(NSF)-IMPACTS Training Grant(DGE-1828149)+6 种基金funded by NSF Dimensions of Biodiversity(DEB 1737898)supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM110523the US Department of Energy Great Lakes Bioenergy Research Center Cooperative Agreement DESC0018409funding from the Department of Biochemistry and Molecular Biology at MSU and support from AgBioResearch(MICL02454)supported in part by the National Science Foundation under Grant number 1737898funding from the University of Georgia,the Georgia Research Alliance,and Georgia Seed Developmentsupport from the NSF under grant number ISO-2029959.
文摘Teucrium chamaedrys,commonly known as wall germander,is a small woody shrub native to the Mediterranean region.Its name is derived from the Greek words meaning‘‘ground oak,’’as its tiny leaves resemble those of an oak tree.Teucrium species are prolific producers of diterpenes,endowing them with valuable properties widely utilized in traditional and modern medicine.Sequencing and assembly of the 3-Gbp tetraploid T.chamaedrys genome revealed 74 diterpene synthase genes,with a substantial number of these genes clustered at four synteny genomic loci,each harboring a copy of a large diterpene biosynthetic gene cluster.Comparative genomics revealed that this cluster is conserved in the closely related species Teucrium marum.Along with the presence of several cytochrome p450 sequences,this region is among the largest biosynthetic gene clusters identified.Teucrium is well known for accumulating clerodane-type diterpenoids,which are produced from a kolavenyl diphosphate precursor.To elucidate the complex biosynthetic pathways of these medicinal compounds,we identified and functionally characterized several kolavenyl diphosphate synthases from T.chamaedrys.The remarkable chemical diversity and tetraploid nature of T.chamaedrys make it a valuable model for studying genomic evolution and adaptation in plants.
基金supported by the Youth Innovation Program of the Chinese Academy of Agricultural Sciences(Y2023QC34)the Natural Science Foundation of Shandong province(ZR2023MC034)+2 种基金the Technological Innovation Project of ECS-CAAS(ECS-KY-N-2024008)the Agricultural Science and Technology Innovation Program(ASTIP-TRIC05-2025)the Central Public-interest Scientific Institution Basal Research Fund(1610232024005,1610232023003).
文摘Northern wild rice(NWR;Zizania palustris L.),an annual aquatic plant in the Poaceae family,has high economic importance due to its nutrient-rich grains.However,the existing NWR genome assembly for this species has severe fragmentation and incomplete gene representation.A near-complete genome was assembled in this study to provide a high-quality genomic reference for NWR-associated research.The assembled genome exhibited a total contig length of 1.41 Gb and a contig N50 of 109.22 Mb.Overall,a 73.60%repetitive sequence content was identified and 47,804 genes predicted.Phylogenetic analysis indicated that Z.palustris was most closely related to Zizania latifolia,with an estimated divergence time of 4.57–8.15 Mya.Meanwhile,Z.palustris underwent a recent,species-specific long terminal repeat(LTR)expansion,associated with its larger genome size.We identified two genomic blocks in the Z.palustris and Z.latifolia genomes that exhibit strong synteny with the rice phytocassane biosynthetic gene cluster.The centromeric satellite repeats in Z.palustris identified in this study primarily comprised a 145 bp repetitive unit.The findings also revealed centromere homogenisation and rearrangement accompanied by LTR invasion in NWR.Among the genes missing in the previous NWR genome,we observed LTR insertion events that resulted in expanded gene lengths in our updated NWR genome.The present updated NWR genome provides a valuable resource for crop genetic improvement,functional gene discovery,and research on critical biological processes.
基金This work was supported by grants from the Zhejiang Natural Science Foundation(LZ17C130001)the Jiangsu Collaborative Innovation Center for Modern Crop Production,111 Project(B17039).
文摘Benzoxazinoids are a class of protective and allelopathic plant secondary metabolites that have been identified in multiple grass species and are encoded by the Bx biosynthetic gene cluster(BGC)in maize.Data mining of 41 high-quality grass genomes identified complete Bx clusters(containing genes Bx1–Bx5 and Bx8)in three genera(Zea,Echinochloa,and Dichanthelium)of Panicoideae and partial clusters in Triticeae.The Bx cluster probably originated from gene duplication and chromosomal translocation of native homologs of Bx genes.An ancient Bx cluster that included additional Bx genes(e.g.,Bx6)is presumed to have been present in ancestral Panicoideae.The ancient Bx cluster was putatively gained by the Triticeae ancestor via horizontal transfer(HT)from the ancestral Panicoideae and later separated into multiple segments on different chromosomes.Bx6 appears to have been under less constrained selection compared with the Bx cluster during the evolution of Panicoideae,as evidenced by the fact that it was translocated away from the Bx cluster in Zea mays,moved to other chromosomes in Echinochloa,and even lost in Dichanthelium.Further investigations indicate that purifying selection and polyploidization have shaped the evolutionary trajectory of Bx clusters in the grass family.This study provides the first candidate case of HT of a BGC between plants and sheds new light on the evolution of BGCs.
基金the National Key R&D Program of China(grant No.2021YFC2103500)National Natural Science Foundation of China(grant No.22078169)+1 种基金Natural Science Foundation of Shandong Province,China(ZR2021MC074,ZR2020MC008)Shandong Provincial Key Research and Development Plan(2021ZDSYS28).
文摘Methylobacterium species,the representative bacteria distributed in phyllosphere region of plants,often synthesize carotenoids to resist harmful UV radiations.Methylobacterium extorquens is known to produce a carotenoid pigment and recent research revealed that this carotenoid has a C_(30) backbone.However,its exact structure remains unknown.In the present study,the carotenoid produced by M.extorquens AM1 was isolated and its structure was determined as 4-[2-O-11Z-octadecenoyl-β-glucopyranosyl]-4,4′-diapolycopenedioc acid(1),a glycosylated C_(30) carotenoid.Furthermore,the genes related to the C_(30)carotenoid synthesis were investigated.Squalene,the precursor of the C_(30) carotenoid,is synthesized by the co-occurrence of META1p1815,META1p1816 and META1p1817.Further overexpression of the genes related to squalene synthesis improved the titer of carotenoid 1.By using gene deletion and gene complementation experiments,the glycosyltransferase META1p3663 and acyltransferase META1p3664 were firstly confirmed to catalyze the tailoring steps from 4,4′-diapolycopene-4,4′-dioic acid to carotenoid 1.In conclusion,the structure and biosynthetic genes of carotenoid 1 produced by M.extorquens AM1 were firstly characterized in this work,which shed lights on engineering M.extorquens AM1 for producing carotenoid 1 in high yield.
基金supported in part by grants from the National Key Research and Development Program of China(2018YFA0901900)the National Natural Science Foundation of China(22137009)the China Postdoctoral Science Foundation(2020M671271).
文摘A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.
基金funded by an ARC Australian Laureate Fellowship(grant number FL210100071)to JE.FAS is supported by DOST-SEI Foreign Graduate Scholarship Program.
文摘Plants and microbes are closely associated with each other in their ecological niches.Much has been studied about plant-microbe interactions,but little is known about the effect of phytochemicals on microbes at the molecular level.To access the products of cryptic biosynthetic gene clusters in bacteria,we incorporated an organic extract of hibiscus flowers into the culture media of different Actinobacteria isolated from plant rhizospheres.This approach led to the production of broad-spectrum dithiolopyrrolone(DTP)antibiotics,thiolutin(1)and aureothricin(2),by Streptomyces sp.MBN2-2.The compounds from the hibiscus extract responsible for triggering the production of these two DTPs were found to be hibiscus acid dimethyl ester(3)and hydroxycitric acid 1,3-dimethyl ester(4).It was subsequently found that the addition of either Fe2+or Fe3+to culture media induced the production of 1 and 2.The Chrome Azurol S(CAS)assay revealed that 3 and 4 can chelate iron,and therefore,the mechanism leading to the production of thiolutin and aureothricin appears to be related to changes in iron concentration levels.This work supports the idea that phytochemicals can be used to activate the production of cryptic microbial biosynthetic gene clusters and further understand plant-microbe interactions.
基金supported by the National Natural Science Foundation of China(31872617)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-055,2019-I2M-1-005)+1 种基金the National Microbial Resource Center(NMRC-2024-3)the central level,scientific research institutes for basic R&D fund business(3332018097).
文摘Genome mining has revealed that Penicillium spp.possess numerous down-regulated or cryptic biosynthetic gene clusters(BGCs).This finding hinted that our investigation of fungal secondary metabolomes is limited.Herein,we report a genetically-modified activation strategy to characterize the spectrum of sesquiterpenoids produced by Penicillium brasilianum CGMCC 3.4402.The cryptic or down-regulated pathways were stimulated by constitutive expression of pathway-specific regulator gene berA responsible for berkeleyacetals biosynthesis from Neosartorya glabra.Chemical analysis of the extracts from the mutant strain Pb-OE:berA enabled the isolation of two new compounds including one bisabolene-type arpenibisabolane C(1),one daucane-type arpenicarotane C(4),along with four known sesquiterpenoids including arpenibisabolane A(2),eupenicisirenins A(3),arpenicarotane B(5)and aspterric acid(6).The assignments of their structures were elucidated from detailed analyses of spectroscopic data,electronic circular dichroism calculation,and biogenetic considerations.The bioassay of isolated compounds(1-6)exhibited no cytotoxic activities against three tumor cells including MCF-7,HepG2,and A549.Arpenibisabolane C(1)and A(2)showed weak inhibition bioactivities on aquatic pathogens Vibrio owensii and Vibrio algivorus.Moreover,phylogenetic analysis and sequence alignments of crucial sesquiterpene synthases were performed.Based on the chemical structures and biogenetic investigations,a hypothetic pathway of new compounds(1,4)was proposed.
文摘Bacteria living in sediments play essential roles in marine ecosystems and deeper insights into the ecology and biogeochemistry of these largely unexplored organisms can be obtained from‘omics’approaches.Here,we characterized metagenome-assembled-genomes(MAGs)from the surface sediment microbes of the Venice Lagoon(northern Adriatic Sea)in distinct sub-basins exposed to various natural and anthropogenic pressures.MAGs were explored for biodiversity,major marine metabolic processes,anthropogenic activity-related functions,adaptations at the microscale,and biosynthetic gene clusters.Starting from 126 MAGs,a non-redundant dataset of 58 was compiled,the majority of which(35)belonged to(Alpha-and Gamma-)Proteobacteria.Within the broad microbial metabolic repertoire(including C,N,and S metabolisms)the potential to live without oxygen emerged as one of the most important features.Mixotrophy was also found as a successful lifestyle.Cluster analysis showed that different MAGs encoded the same metabolic patterns(e.g.,C fixation,sulfate oxidation)thus suggesting metabolic redundancy.Antibiotic and toxic compounds resistance genes were coupled,a condition that could promote the spreading of these genetic traits.MAGs showed a high biosynthetic potential related to antimicrobial and biotechnological classes and to organism defense and interactions as well as adaptive strategies for micronutrient uptake and cellular detoxification.Our results highlighted that bacteria living in an impacted environment,such as the surface sediments of the Venice Lagoon,may benefit from metabolic plasticity as well as from the synthesis of a wide array of secondary metabolites,promoting ecosystem resilience and stability toward environmental pressures.
基金supported by the National Natural Science Foundation of China(grant nos.81973435 and 81473313)the National Natural Science Foundation for Young Scientists of China(grant no.81903756)+2 种基金the Open Project of the Natural Science Foundation of Nanjing University of Chinese Medicine(no.NZY81903756)research on ecological planting and quality assurance of Jiangsu Dao-di herbs(2021)and a Jiangsu Government Scholarship for Overseas Studies(JS-2020-044).We also acknowledge support from the BBSRC(BBN006452/1)and UKRI(MR/S01862X/1).
文摘Biosynthetic gene clusters(BGCs)are regions of a genome where genes involved in a biosynthetic pathway are in proximity.The origin and evolution of plant BGCs as well as their role in specialized metabolism remain largely unclear.In this study,we have assembled a chromosome-scale genome of Japanese catnip(Schizonepeta tenuifolia)and discovered a BGC that contains multiple copies of genes involved in four adjacent steps in the biosynthesis of p-menthane monoterpenoids.This BGC has an unprecedented bipartite structure,with mirrored biosynthetic regions separated by 260 kilobases.This bipartite BGC includes identical copies of a gene encoding an old yellow enzyme,a type of flavin-dependent reductase.In vitro assays and virus-induced gene silencing revealed that this gene encodes the missing isopiperitenone reductase.This enzyme evolved from a completely different enzyme family to isopiperitenone reductase from closely related Mentha spp.,indicating convergent evolution of this pathway step.Phylogenomic analysis revealed that this bipartite BGC has emerged uniquely in the S.tenuifolia lineage and through insertion of pathway genes into a region rich in monoterpene synthases.The cluster gained its bipartite structure via an inverted duplication.The discovered bipartite BGC for p-menthane biosynthesis in S.tenuifolia has similarities to the recently described duplicated p-menthane biosynthesis gene pairs in the Mentha longifolia genome,providing an example of the convergent evolution of gene order.This work expands our understanding of plant BGCs with respect to both form and evolution,and highlights the power of BGCs for gene discovery in plant biosynthetic pathways.
基金grants to National Institute of Immunology,New Delhi from Department of Biotechnology(DBT),Government of India.DM also acknowledges financial support from DBT,India under BTIS project(BT/BI/03/009/2002)Bioinformatics R&D grant(BT/PR13526/BID/07/311/2010).
文摘In silico methods for linking genomic space to chemical space have played a crucial role in genomics driven discovery of new natural products as well as biosynthesis of altered natural products by engineering of biosynthetic pathways.Here we give an overview of available computational tools and then briefly describe a novel computational framework,namely retro-biosynthetic enumeration of biosynthetic reactions,which can add to the repertoire of computational tools available for connecting natural products to their biosynthetic gene clusters.Most of the currently available bioinformatics tools for analysis of secondary metabolite biosynthetic gene clusters utilize the“Genes to Metabolites”approach.In contrast to the“Genes to Metabolites”approach,the“Metabolites to Genes”or retro-biosynthetic approach would involve enumerating the various biochemical transformations or enzymatic reactions which would generate the given chemical moiety starting from a set of precursor molecules and identifying enzymatic domains which can potentially catalyze the enumerated biochemical transformations.In this article,we first give a brief overview of the presently available in silico tools and approaches for analysis of secondary metabolite biosynthetic pathways.We also discuss our preliminary work on development of algorithms for retro-biosynthetic enumeration of biochemical transformations to formulate a novel computational method for identifying genes associated with biosynthesis of a given polyketide or nonribosomal peptide.
基金This work was supported by the National Basic Research Program(973 Program)the National Programs for High Technology Research Development Program(863 Program)from the Ministry of Science and Technology,the National Science Foundation of China,the Ministry of Education,the Science and Technology Commission of Shanghai Municipality,and Shanghai Leading Academic Discipline Project B203.
文摘Tunicamycin,a potent reversible translocase I inhibitor,is produced by several Actinomycetes species.The tunicamycin structure is highly unusual,and contains an 11-carbon dialdose sugar and anα,β-1″,11′-glycosidic linkage.Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression(HHE)strategy combined with a bioassay.Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains,demonstrating the role of the genes for the biosynthesis of tunicamycins.Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes(tunA–tunL).Amongst these is a putative radical SAM enzyme(Tun B)with a potentially unique role in biosynthetic carbon-carbon bond formation.Hence,a seven-step novel pathway is proposed for tunicamycin biosynthesis.Moreover,two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827.These data provide clarification of the novel mechanisms for tunicamycin biosynthesis,and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.
基金supported by the Shanghai Municipal Science and Technology Major Project,National Key Research and Development Program of China(grant No.2019YFA0905400)National Natural Science Foundation of China(grant No.31830104)to L.B.
文摘Natural products(NPs)afforded by living-beings,especially by microscopic species,represent invaluable and indispensable reservoirs for drug leads in clinical practice.With the rapid advancement in sequencing technology and bioinformatics,the ever-increasing number of microbial biosynthetic gene clusters(BGCs)were decrypted,while a great deal of BGCs remain cryptic or inactive under standard laboratory culture conditions.Addressing this dilemma requires innovative tactics to awaken quiescence of BGCs by releasing the potential of microbial secondary metabolism for mining novel NPs.In this study,a universal strategy was proposed to induce the expression of silent BGCs by leveraging the dynamic interactions among coexisting microbial neighbors within a microbiota.This approach involves the deconstruction/reconstruction of binary interactions among the coex-isting neighbors to create a pipeline for BGCs arousing.Coupled with the acquisition of 2760 microbial in-dividuals from the Apocynum venetum(Luobuma,LBM)phyllosphere in a successive dilution procedure,44 culturable isolates were screened using binary interaction,in which 12.6%pairs demonstrated potent mutual interacting effects.Furthermore,after selecting the four most promising isolates,a full-scale metabolic inspection was conducted,in which 25.3%of the interacting pairs showcased significant metabolomic variations with de-cryptic activities.Notably,with the aid of visualization of IMS technology,one of the physiologically functional entities,the bactericidal agent resistomycin,was elucidated from the core interacting pair between the co-culture of the Streptomyces sp.LBM_605 and the Rhodococcus sp.LBM_791.This study highlights the intrinsic interactions among coexisting microorganisms within a phyllosphere microbiota as novel avenues for exploring and har-nessing NPs.
基金The Z.L.laboratory is supported by a startup grant provided by Shanghai Jiao Tong University,School of Agriculture and Biology and the Shanghai Pujiang Program(20PJ1405900).
文摘Plants produce a remarkable diversity of structurally and functionally diverse natural chemicals that serve as adaptive compounds throughout their life cycles.However,unlocking this metabolic diversity is significantly impeded by the size,complexity,and abundant repetitive elements of typical plant genomes.As genome sequencing becomes routine,we anticipate that links between metabolic diversity and genetic variation will be strengthened.In addition,an ever-increasing number of plant genomes have revealed that biosynthetic gene clusters are not only a hallmark of microbes and fungi;gene clusters for various classes of compounds have also been found in plants,and many are associated with important agronomic traits.We present recent examples of plant metabolic diversification that have been discovered through the exploration and exploitation of various genomic and pan-genomic data.We also draw attention to the fundamental genomic and pan-genomic basis of plant chemodiversity and discuss challenges and future perspectives for investigating metabolic diversity in the coming pan-genomics era.
基金This work was supported by the European Commission Marie Curie Initial Training Network Quantfung(FP7-People-2013-ITN,Grant 607332).
文摘The genomic era has revolutionized research on secondary metabolites and bioinformatics methods have in recent years revived the antibiotic discovery process after decades with only few new active molecules being identified.New computational tools are driven by genomics and metabolomics analysis,and enables rapid identification of novel secondary metabolites.To translate this increased discovery rate into industrial exploitation,it is necessary to integrate secondary metabolite pathways in the metabolic engineering process.In this review,we will describe the novel advances in discovery of secondary metabolites produced by filamentous fungi,highlight the utilization of genome-scale metabolic models(GEMs)in the design of fungal cell factories for the production of secondary metabolites and review strategies for optimizing secondary metabolite production through the construction of high yielding platform cell factories.
基金supported by the National Key Research and Development Program of China(2023YFC2706503)the National Natural Science Foundation of China(32370720)+9 种基金Beihang University&Capital Medical University Plan(BHME-201904)the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE,ECNU,Key Laboratory of MEA,Ministry of Education,ECNU,Key Laboratory of Ecology and Energy Saving Study of Dense Habitat(Tongji University),Ministry of Education-Shanghai Tongji Urban Planning&Design Institute Co.,Ltd Joint Research Project(KY-2022-LH-A03)Shanghai Tongji Urban Planning&Design Institute Co.,Ltd-China Intelligent Urbanization Co-creation Center for High Density Region Research Project(KY-2022-PT-A02)the Irma T.Hirschl and Monique Weill-Caulier Charitable TrustsBert L and N Kuggie Vallee Foundationthe World Quant FoundationThe Pershing Square Sohn Cancer Research Alliancethe National Institutes of Health(R01AI151059)the National Science Foundation(1840275)the Alfred P.Sloan Foundation(G-2015-13964)。
文摘Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.
基金This work was supported by the National Key R&D Program of China(2018YFA0903300)the Natural Science Foundation of Tianjin Province(19JCYBJC24200)the National Natural Science Foundation of China(81502966).
文摘Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compounds with high yields.This review summarized the commonly used regulatory strategies for natural products discovery and overproduction in Streptomyces from three main aspects,including regulator-related strategies,promoter engineering,as well as other strategies employing transposons,signal factors,or feedback regulations.It is expected that the metabolic regulation network of Streptomyces will be elucidated more comprehensively to shed light on natural products research in the future.
