Metagenomics has opened new avenues for exploring the genetic potential of uncultured microorganisms,which may serve as promising sources of enzymes and natural products for industrial applications.Identifying enzymes...Metagenomics has opened new avenues for exploring the genetic potential of uncultured microorganisms,which may serve as promising sources of enzymes and natural products for industrial applications.Identifying enzymes with improved catalytic properties from the vast amount of available metagenomic data poses a significant challenge that demands the development of novel computational and functional screening tools.The catalytic properties of all enzymes are primarily dictated by their structures,which are predominantly determined by their amino acid sequences.However,this aspect has not been fully considered in the enzyme bioprospecting processes.With the accumulating number of available enzyme sequences and the increasing demand for discovering novel biocatalysts,structural and functional modeling can be employed to identify potential enzymes with novel catalytic properties.Recent efforts to discover new polysaccharide-degrading enzymes from rumen metagenome data using homology-based searches and machine learning-based models have shown significant promise.Here,we will explore various computational approaches that can be employed to screen and shortlist metagenome-derived enzymes as potential biocatalyst candidates,in conjunction with the wet lab analytical methods traditionally used for enzyme characterization.展开更多
Medicinal plants are an excellent source of structurally diverse,bio-active compounds with potential in the fight against cancer.One of the most promising is Scutellaria barbata,prescribed traditionally for the treatm...Medicinal plants are an excellent source of structurally diverse,bio-active compounds with potential in the fight against cancer.One of the most promising is Scutellaria barbata,prescribed traditionally for the treatment of cancers.Scutebarbatine A is the major diterpenoid,produced in specialized large,peltate trichomes on leaves of S.barbata.It induces dose-dependent apoptosis,specifically in cancer cells.The major class of proteins down-regulated are pro-survival proteins,the Inhibitors of Apoptosis(IAPs),and IAP regulating proteins.We propose that scutebarbatine A works by releasing the molecular brakes(the IAPs)on apoptosis in cell death-evading cancer cells.Comparison between the cytotoxicity of methanolic extracts of S.barbata leaves and decoctions(Ban Zhi Lian)prepared traditionally,showed substantially different chemical compositions and differential induction of apoptosis.Analyses suggest polyvalency between the constituents in both extracts,and ways to produce enhanced chemopreventive preparations for the treatment of cancer.展开更多
The gut-brain axis(GBA)is a crucial connection that enables bidirectional communication between the central nervous system and gastrointestinal tract.Serotonin is a tryptophan(Trp)metabolite and an important gastroint...The gut-brain axis(GBA)is a crucial connection that enables bidirectional communication between the central nervous system and gastrointestinal tract.Serotonin is a tryptophan(Trp)metabolite and an important gastrointestinal signaling molecule.Kynurenine and indole derivatives mediate the central nervous system,thereby affecting neurological diseases.The gut microbiota has direct or indirect impact on Trp metabolism.Different genera of gut microbiota affect Trp metabolites in different ways,thus changing the communication between the brain and gastrointestinal tract.This review highlights the triangular relationship between the GBA,Trp metabolism,and gut microbiota and summarizes the types of relevant gut microbiota genera involved in this triangular relationship.By modulating the gut microbiota through probiotics,dietary interventions,fecal microbiota transplantation,and other methods,improving Trp metabolism and thereby influencing metabolites provides potential targets for treating GBA-related diseases.展开更多
Hyaluronic acid(HA),a linear glycosaminoglycan polymer,is an inherent carbon source for gut microbiota and is capable of mitigating host inflammation by modulating gut microbiota.The length of hyaluronan can range fro...Hyaluronic acid(HA),a linear glycosaminoglycan polymer,is an inherent carbon source for gut microbiota and is capable of mitigating host inflammation by modulating gut microbiota.The length of hyaluronan can range from an oligomer to an extremely long-form up to millions of Daltons,and its biological functions depend on its molecular mass[1,2].Presently,the precise mechanisms through which HA of varying molecular weights alleviates inflammation by modulating the gut microbiota remain unclear[3].展开更多
In a recent Science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimula...In a recent Science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.展开更多
基金Funding was provided by the Agricultural Biotechnology Research Institute of Iran(ABRII),Swedish Research Council(Vetenskapsrådet grant no.:2017-05019)the BBSRC Institute Strategic Programme Gut Microbes and Health(BB/r012490/1,its constituent project BBS/e/F/000Pr10355).
文摘Metagenomics has opened new avenues for exploring the genetic potential of uncultured microorganisms,which may serve as promising sources of enzymes and natural products for industrial applications.Identifying enzymes with improved catalytic properties from the vast amount of available metagenomic data poses a significant challenge that demands the development of novel computational and functional screening tools.The catalytic properties of all enzymes are primarily dictated by their structures,which are predominantly determined by their amino acid sequences.However,this aspect has not been fully considered in the enzyme bioprospecting processes.With the accumulating number of available enzyme sequences and the increasing demand for discovering novel biocatalysts,structural and functional modeling can be employed to identify potential enzymes with novel catalytic properties.Recent efforts to discover new polysaccharide-degrading enzymes from rumen metagenome data using homology-based searches and machine learning-based models have shown significant promise.Here,we will explore various computational approaches that can be employed to screen and shortlist metagenome-derived enzymes as potential biocatalyst candidates,in conjunction with the wet lab analytical methods traditionally used for enzyme characterization.
基金the Royal Society for a Newton Advanced Fellowship awarded to ECT(NAF\R2\192001)CEPAMS Funding(Project CPM19)for support of a collaboration project'Scutellaria Anticancer Metabolites'for E.C.T.,C.M.,M-J.R.H.,J.F.and Q.Z.C.M.,M.T.,E.B.,M.R.,G.S.,L.H..and J.L.were also supported by the Institute Strategic Programme‘Molecules from Nature’(BB/P012523/1)+4 种基金the UK Biotechnology and Biological Sciences Research Council.MZ was supported by a CSC visiting scholarship and by the Natural Science Foundation of Zhejiang Province,China(LY21H280009)We thank CAS for the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB27020204)International Partnership Program of CAS(153D31KYSB20160074)we gratefully acknowledge the Ministry of Science and Technology for Foreign Expert Project 2019(G20190113016)the Science and Technology Commission of Shanghai Municipality for Shanghai Talent Recruitment Program 2018 and funds from National Key Laboratory of Plant Molecular Genetics and Shanghai Institute of Plant Physiology and Ecology to ECT for support of this project.
文摘Medicinal plants are an excellent source of structurally diverse,bio-active compounds with potential in the fight against cancer.One of the most promising is Scutellaria barbata,prescribed traditionally for the treatment of cancers.Scutebarbatine A is the major diterpenoid,produced in specialized large,peltate trichomes on leaves of S.barbata.It induces dose-dependent apoptosis,specifically in cancer cells.The major class of proteins down-regulated are pro-survival proteins,the Inhibitors of Apoptosis(IAPs),and IAP regulating proteins.We propose that scutebarbatine A works by releasing the molecular brakes(the IAPs)on apoptosis in cell death-evading cancer cells.Comparison between the cytotoxicity of methanolic extracts of S.barbata leaves and decoctions(Ban Zhi Lian)prepared traditionally,showed substantially different chemical compositions and differential induction of apoptosis.Analyses suggest polyvalency between the constituents in both extracts,and ways to produce enhanced chemopreventive preparations for the treatment of cancer.
基金supported by the National Natural Science Foundation of China(32372296)Natural Science Foundation of Jiangsu Province(BK20220155,BE2021623)Collaborative Innovation Center of Food Safety and Quality.
文摘The gut-brain axis(GBA)is a crucial connection that enables bidirectional communication between the central nervous system and gastrointestinal tract.Serotonin is a tryptophan(Trp)metabolite and an important gastrointestinal signaling molecule.Kynurenine and indole derivatives mediate the central nervous system,thereby affecting neurological diseases.The gut microbiota has direct or indirect impact on Trp metabolism.Different genera of gut microbiota affect Trp metabolites in different ways,thus changing the communication between the brain and gastrointestinal tract.This review highlights the triangular relationship between the GBA,Trp metabolism,and gut microbiota and summarizes the types of relevant gut microbiota genera involved in this triangular relationship.By modulating the gut microbiota through probiotics,dietary interventions,fecal microbiota transplantation,and other methods,improving Trp metabolism and thereby influencing metabolites provides potential targets for treating GBA-related diseases.
基金National Natural Science Foundation of China General Program(32372296)Natural Science Foundation of Jiangsu Province(BK20220155)+2 种基金National Key Research and Development Project of China(2022YFF1100203)Key Scientific and Technological Research Projects in the Key Areas of the Xinjiang Production and Construction Corps(2018AB010)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Hyaluronic acid(HA),a linear glycosaminoglycan polymer,is an inherent carbon source for gut microbiota and is capable of mitigating host inflammation by modulating gut microbiota.The length of hyaluronan can range from an oligomer to an extremely long-form up to millions of Daltons,and its biological functions depend on its molecular mass[1,2].Presently,the precise mechanisms through which HA of varying molecular weights alleviates inflammation by modulating the gut microbiota remain unclear[3].
基金supported by the National Research,Development and Innovation Office of Hungary(grant number:NKFI FK134684)project TKP2021-EGA-28 was implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research,Development and Innovation Fund,financed under the TKP2021-EGA funding scheme+4 种基金The work of T.K.was supported by the UKRI BBSRC Institute Strategic Programme Food Microbiome and Health BB/X011054/1 and its constituent project BBS/E/F/000PR13631T.K.was also supported by the NIHR Imperial Biomedical Research Centre Organoid FacilityThe views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social CareT.V.was supported by grant OTKA(Hungarian Scientific Research Fund,K132439)HUN-REN-ELTE Genetics Research Group(01062).
文摘In a recent Science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.
