In order to solve the citrus peel resource waste problem protopectinase-overproducing strain CD-01 for pectin production and minimize the drawbacks of chemical extraction of pectin, a was isolated from a pit soil dump...In order to solve the citrus peel resource waste problem protopectinase-overproducing strain CD-01 for pectin production and minimize the drawbacks of chemical extraction of pectin, a was isolated from a pit soil dumped with perished orange in Changde City, Hunan Province of China. The strain CD-01 had the same morphology and 28S rRNA gene sequence （FJ184995） as that of Aspergillus niger （ATCC 64028）. It was thus identified and named as Aspergillus niger CD-01. The fermentation condition was optimized based on L9（34） orthogonal experimental design and the variances analyses. The results show that the optimal condition for producing pectin is as follows： time 36 h, temperature 35 ℃, pH 5, and urea as the nitrogen source. Under this condition, the pectin yield can reach up to 24.5%. This shows a great potential of Aspergillus niger CD-01 in pectin extraction from citrus.展开更多
The global demand for large-scale and cost-effective production of high-quality protein has become increasingly urgent,with microbial protein derived from methanol being recognized as a promising solution.Among 50 met...The global demand for large-scale and cost-effective production of high-quality protein has become increasingly urgent,with microbial protein derived from methanol being recognized as a promising solution.Among 50 methylotrophic strains,Methylophilus sp.HN238 was selected for its capability to utilize methanol as the sole carbon.Through optimization of the medium composition,a 387.30%increase in protein yield was achieved during shake-flask fermentation.Subsequent scale-up to a 5 L bioreactor resulted in a protein content of 57.30%.Amino acid composition analysis revealed that 18 amino acids were quantitatively detectable in the protein,with essential amino acids accounting for 44.10%of the total composition,thereby demonstrating compliance with the World Health Organization(WHO)standards for high-quality protein.Tran-scriptomic differential analysis was conducted to investigate the metabolic response of Methylophilus sp.HN238 to methanol concentrations(10 g/L vs.50 g/L).It was observed that high methanol concentrations promoted the upregulation of methanol dehydrogenase(MDH)encoded by the maxI gene,while formaldehyde dehydrogenase(FLD)and cytochrome c(cyt c)were downregulated.This regulatory imbalance was associated with intracellular formaldehyde accumulation,impaired electron transport chain efficiency,oxidative stress,and subsequent inhibition of cellular growth.The study not only validated the potential of Methylophilus sp.HN238 for protein production with high methanol concentrations but also provided critical insights into metabolic engineering strategies to enhance methanol-to-biomass conversion efficiency.展开更多
Fidaxomicin,a macrolide antibiotic,is widely used to treat Clostridioides difficile infection(CDI).It demonstrats significantly higher clinical efficacy than vancomycin and metronidazole.However,the large-scale indust...Fidaxomicin,a macrolide antibiotic,is widely used to treat Clostridioides difficile infection(CDI).It demonstrats significantly higher clinical efficacy than vancomycin and metronidazole.However,the large-scale industrial production of it remains a significant challenge because of the low fermentation yields.In this study,we chosen the strain OE-R1/WT as the starting strain,in which a pathway-specific positive regulatory factor fadR1 was overexpressed.By using the kanR/gusA dual-reporter system and ARTP mutagenesis,we screened a high-yield strain,PA-13,which produced 757.34 mg/L of fidaxomicin,representing a 5.5-fold increase over OE-R1/WT and having enhanced genetic stability.Furthermore,by overexpressing two methyltransferases within the biosynthetic cluster and supplementing with exogenous DMSO,we further increased the production of fidax-omicin to 929.17 mg/L,while reducing the accumulation of the major by-product to 20.9%.Finally,through the optimization of fermentation strategies at both the shake flask and 15 L fermenter levels,we achieved a final yield of 3949.05 mg/L in the 15 L fermenter,which represents the highest yield up to date.Our study represents the first successful enhancement of fidaxomicin production in Actinoplanes deccanensis to over 3.9 g/L in a 15 L fermenter,establishing a robust foundation for industrial-scale fermentation.Additionally,it provides significant insights for the development of high-yield strains in other actinomycetes.展开更多
A sequential statistical approach was applied to optimizing the fermentation medium of epothilones（Epos） production by means of a mutant which was obtained by treating polyangium cellulosum ATCC 15384 with nitrite a...A sequential statistical approach was applied to optimizing the fermentation medium of epothilones（Epos） production by means of a mutant which was obtained by treating polyangium cellulosum ATCC 15384 with nitrite and ultraviolet. The effects of different carbon sources and nitrogen sources on the fermentation medium were tested, and the suitable ones were selected. Then a uniform design was employed to design the experiments. A linear model was developed for identifying the significant components in fermentation medium, while a third degree polynomial model was used for studying the relationship between the concentration of the components in fermentation medium and the yield of Epos（YEPs）. A pattern search method was used for searching the optimum fermentation medium in the test space, which was as follows（g/L）： potassium nitrate 8.00, soybean peptone 17.60, potassium hydrogen phos- phate 1.00, beef extraction 6.46, yeast extraction 1.00, calcium chloride 0.25, sodium chloride 1.00 and ferric chloride 0.02. The optimum fermentation medium was expected to result in a yield of Epos（YEPs） of 2.48 mg/L. The validation experiments with the optimum medium were performed in triplicate and the average yield of Epos was 2.45 mg/L which was 7.78 times higher than that of Epos prepared without optimization.展开更多
Chinese rice wine making is a typical simultaneous saccharification and fermentation （SSF） process. During the fermentation process, temperature is one of the key parameters which decide the quality of Chinese rice ...Chinese rice wine making is a typical simultaneous saccharification and fermentation （SSF） process. During the fermentation process, temperature is one of the key parameters which decide the quality of Chinese rice wine. To optimize the SSF process for Chinese rice wine brewing, the effects of temperature on the kinetic parameters of yeast growth and ethanol production at various temperatures were determined in batch cultures using a mathematical model. The kinetic parameters as a function of temperature were evaluated using the software Origin8.0. Combing these functions with the mathematical model, an appropriate form of the model equations for the SSF considering the effects of temperature were developed. The kinetic parameters were found to fit the experimental data satisfactorily with the developed temperature-dependent model. The temperature profile for maximizing the ethanol production for rice wine fermentation was determined by genetic algorithm. The optimum temperature profile began at a low temperature of 26℃ up to 30 h. The operating temperature increased rapidly to 31.9 ℃, and then decreased slowly to 18℃ at 65 h. Thereafter, the temperature was maintained at 18 ℃ until the end of fermentation. A maximum ethanol production of 89.3 g.L 1 was attained. Conceivably, our model would facilitate the improvement of Chinese rice wine production at the industrial scale.展开更多
A strain isolated from the fruiting body of a fungus parasitized on Elaphomyces was identified as Cordyceps ophioglossoides based on the morphological characteristics and the analysis of ITS-5.8s rDNA sequence. The op...A strain isolated from the fruiting body of a fungus parasitized on Elaphomyces was identified as Cordyceps ophioglossoides based on the morphological characteristics and the analysis of ITS-5.8s rDNA sequence. The optimal medium, composition （g·L^-1）, containing sucrose 66.0, yeast powder 10.0, silkworm chrysalises digest 30.0, MgSO4· 7H2O 0.4, and KH2PO4 0.4, Was found using fractional factorial design ancl a central composite design, and the optimization of cultural conditions obtained a result of seed age 6 days, inoculum size 6% （by volume）, initial pH 5.6, temperature 24℃, shaking speed 160 ·＇min^-1 by one-factor-at-a-time method. The maximum biomass reached about 20.2 g·L^-1 after 90 hours culture under the optimal conditions. Elementary nharmaeclogical actlwtties showed that mycelia of C. ophioglossoides L2 from submerged culture promoted Uterus growth in estrogen- depleted mice. In the 15-litre scale-up fermentation, the mycelial biomass was around 19.1 g·L^-1, indicating a promising prospect for this biotechnoloagy and the potency to develoo its medical value.展开更多
[Objective]This study aimed to improve the yield of bacteriocins from lactic acid bacteria by optimizing the fermentation process for production of bacteriocins from lactic acid bacteria.[Method]By single-factor analy...[Objective]This study aimed to improve the yield of bacteriocins from lactic acid bacteria by optimizing the fermentation process for production of bacteriocins from lactic acid bacteria.[Method]By single-factor analysis,fermentation temperature,seed age,inoculation volume,fermentation duration and fermentation media p H were optimized to determine the best fermentation process.The inhibitory zone of bacteriocins from lactic acid bacteria was analyzed with oxford cup method,based on which the fermentation process was evaluated.[Result]The optimal fermentation process was optimized：fermentation temperature 37℃,seed age 14 h,inoculation volume 2%,fermentation duration 48 h,fermentation media p H 5.0.[Conclusion]Under the optimized fermentation conditions,the yield of bacteriocins from lactic acid bacteria was improved significantly.展开更多
Trichoderma-based formulations are applied as commercial biocontrol agents for soil-borne plant path- ogens. Chlamydospores are active propagules in Trichoderma spp., but their production is currently limited due to a...Trichoderma-based formulations are applied as commercial biocontrol agents for soil-borne plant path- ogens. Chlamydospores are active propagules in Trichoderma spp., but their production is currently limited due to a lack of optimal liquid fermentation technology. In this study, we explored response surface methodologies for opti- mizing fermentation technology in Trichoderma SH2303. Our initial studies, using the Plackett-Burman design, iden- tified cornmeal, glycerol, and initial pH levels as the most significant factors （P〈0.05） for enhancing the production of chlamydospores. Subsequently, we applied the Box-Behnken design to study the interactions between, and optimal levels of, a number of factors in chlamydospore production. These statistically predicted results indicated that the highest number of chlamydospores （3.6×108 spores/ml） would be obtained under the following condition： corn flour 62.86 g/L, glycerol 7.54 ml/L, pH 4.17, and 6-d incubation in liquid fermentation. We validated these predicted values via three repeated experiments using the optimal culture and achieved maximum chlamydospores of 4.5×108 spores/ml, which approximately a 8-fold increase in the number of chlamydospores produced by T. harzianurn SH2303 compared with that before optimization. These optimized values could help make chlamydospore production cost-efficient in the future development of novel biocontrol agents.展开更多
Strain of Pseudomonas Lip35 producing lipase was isolated in a refrigerator. Lipase production and characterization of this strain were investigated under different conditions. The Pseudomonas was cultivated in shakin...Strain of Pseudomonas Lip35 producing lipase was isolated in a refrigerator. Lipase production and characterization of this strain were investigated under different conditions. The Pseudomonas was cultivated in shaking flasks in a fermentation medium in various nutritional and physical environments. Lipase production has been influenced by the presence of yeast-extract, soybean powder, NaCI, and Tween-80. Maximum lipase productivity was obtained when the physical environment of the fermentation medium was optimal for 67 h. The production of lipase reached 58.9 U·mL^-1. The lipase of Pseudomonas Lip35 can be considered to be inducible, but the inducer had little influence on the production of lipase. The lipase was characterized and showed high lipolytic activity from pH 7.5-8.0. The optimum temperature was observed at 20℃ and the thermal inactivation of lipase was obvious at 60℃. The lipase activity was inhibited by K＋, stimulated by Ca^2＋, and thermostability decreased in the presence of Ca^2＋, therefore the lipase was Ca^2＋ -dependent cold-adapted enzyme.展开更多
Foaming reduces the working volume and limits the biosynthesis of macrolide immunosuppressant ascomycin(FK520) in the batch fermentation process of Streptomyces hygroscopicus FS-35 in a 7.5 L bioreactor. To find the r...Foaming reduces the working volume and limits the biosynthesis of macrolide immunosuppressant ascomycin(FK520) in the batch fermentation process of Streptomyces hygroscopicus FS-35 in a 7.5 L bioreactor. To find the relation between FK520 production and foaming, effects of 10 fermentation parameters including organic acids and membrane permeability were investigated. The results suggest that acetate accumulation caused by short period oxygen de ficiency and fast consumption of glucose is the reason for increased foaming and declined FK520 production. Therefore, a fed-batch fermentation strategy was developed to reduce the accumulation of acetate. After optimization, the maximum acetate concentration dropped from 320 mg·L-1to 157 mg·L-1, decreased by 50.8%, and the maximum foam height reduced from 5.32 cm to 3.74 cm, decreased by 29.7%, while the maximum FK520 production increased from 375 mg·L-1to 421 mg·L-1, improved by 12%.展开更多
The soybean cultivar Tadang Muangpai was used to improve the productive quality of Thua-Nao and reduce the concentration of aflatoxin to less than 20 ppb. It was conducted at CMFCRC, Chiangmai, Thailand between Dec. 2...The soybean cultivar Tadang Muangpai was used to improve the productive quality of Thua-Nao and reduce the concentration of aflatoxin to less than 20 ppb. It was conducted at CMFCRC, Chiangmai, Thailand between Dec. 2006 and Mar. 2007. Soybean was boiled for 5 hours and then fermented at different time to create natural bacterial species, mainly Bacillus spp. Thua-Nao could be stored up to 90 days after in storage. Nutritional value, food value, and microorganisms content were investigated during fermentation and storage. Also, aflatoxin content of Thua-Nao was recorded during storage. The results showed that 3 days of soybean fermentation gave the best performance of Thua-Nao in term of nutritional value （protein = 47.12%）, food value, and content of Bacillus spp. （2.78 × 10^9 CFU/g）. Without being harmed from aflatoxin, Thua-Nao could be stored not more than 23 days in normal room （Tmax. = 33.9 ℃, Tmin. = 15.8 ℃） and not more than 36 days in climate-controlled room （Tmax. = 20 ℃, Tmin. = 15 ℃）.展开更多
This study explores the multifaceted regulatory mechanisms of Thermophilic actinomycetes MC-34(TA)in solidstate fermentation of Chinese Baijiu,focusing on their synergistic enhancement of flavor quality.Through monoan...This study explores the multifaceted regulatory mechanisms of Thermophilic actinomycetes MC-34(TA)in solidstate fermentation of Chinese Baijiu,focusing on their synergistic enhancement of flavor quality.Through monoand co-culture fermentation experiments,we revealed that the introduction of thermophilic TA significantly enhances ethanol production(up to 269.56%increase)and sugar-alcohol conversion efficiency(up to 164.41%increase).The activation of interspecies metabolic interaction networks via hydrolase secretion promotes the biosynthesis of 23 characteristic flavor compounds(e.g.,ethyl acetate and isoamyl alcohol),resulting in 20%-30%greater flavor diversity in experimental groups compared to controls.First,TA were found to enrich organic acid profiles(e.g.,isobutyric acid)via cooperative metabolic pathways,concurrently stabilizing environmental pH(50%reduction in pH fluctuation during the late fermentation phase).Furthermore,a novel mechanism was identified:TA inhibitedα-amylase and glucoamylase activities(maximum inhibition rate:98.9%),thereby optimizing substrate utilization efficiency through enzymatic balance regulation.This study challenges the conventional view that TA only participates in terpenoid synthesis.Instead,it innovatively constructs a synergistic metabolic network model involving actinomycetes,yeast,and mold.These findings provide theoretical foundations for synthetic microbial consortia development and modernization of traditional brewing processes,offering critical references for enhancing Baijiu flavor quality and industrial production optimization.展开更多
Stevia rebaudiana was incorporated into kombucha fermentation to evaluate its effects on fermentation dynamics and metabolite production.Fermentation conditions were optimized using response surface methodology and va...Stevia rebaudiana was incorporated into kombucha fermentation to evaluate its effects on fermentation dynamics and metabolite production.Fermentation conditions were optimized using response surface methodology and validated with an electronic tongue system.Volatile compounds in kombucha samples with and without Stevia rebaudiana were characterized via gas chromatography-mass spectrometry(GC-MS).Metagenomic analysis identified Komagataeibacter,Brettanomyces,and Gluconobacter as the dominant genera in both sample types,and their correlations with volatile compounds were visualized through heatmap analysis.Untargeted metabolomics revealed the formation and transformation of key metabolites throughout fermentation,providing insights into changes in total phenolic and flavonoid contents.These findings offer a mechanistic understanding of how Stevia rebaudiana modulates kombucha fermentation,flavor development,and bioactive compound production.展开更多
Sugar polyols,including xylitol,erythritol,mannitol and sorbitol are vital nutritional sweeteners having significant applications across various sectors like food,pharmaceuticals,and cosmetics.Metabolic engineering in...Sugar polyols,including xylitol,erythritol,mannitol and sorbitol are vital nutritional sweeteners having significant applications across various sectors like food,pharmaceuticals,and cosmetics.Metabolic engineering in microbes is a center of attraction to produce value-added products from the lignocellulosic biomass.Clustered regularly interspaced short palindromic repeats(CRISPR)/Cas9 has emerged as a powerful and transformative platform in molecular biology,offering innovative solutions for enhancing the biosynthesis of sugar polyols,paving the way for more efficient and cost-effective production methods.This review aims to offer a thorough overview of CRISPR/Cas9 technology and its role in enhancing production of sugar polyols in microbial systems.It focuses on recent advancements and optimization strategies for improving polyol biosynthesis and productivity through CRISPR/Cas9 based gene editing and fermentation process optimization.The review highlights several successful implementations of CRISPR/Cas9 technology in modifying biosynthetic pathways for sugar polyol production in microbes.Continued research and development in this area are likely to lead to further improvements in efficiency and scalability,benefiting various industries particularly food and pharmaceutical industry that rely on these valuable compounds.展开更多
Astaxanthin,as a natural keto-carotenoid,demonstrates remarkable antioxidant properties.However,the naturally occurring trans-structured free astaxanthin is limited by restricted natural availability and low in-dustri...Astaxanthin,as a natural keto-carotenoid,demonstrates remarkable antioxidant properties.However,the naturally occurring trans-structured free astaxanthin is limited by restricted natural availability and low in-dustrial production yield.Furthermore,its molecular architecture rich in unsaturated double bonds and inherent hydrophobicity critically undermines its stability and bioavailability.In this study,an integrated strategy spanning from production enhancement to functional delivery was established.Xanthophyllomyces dendrorhous,a red yeast,was used to ferment Limnospira platensis,with fermentation parameters systematically optimized to promote astaxanthin accumulation.Subsequently,astaxanthin produced from the optimized fermentation pro-cess was extracted and formulated into two types of astaxanthin-loaded nanoparticles,whose antioxidant ac-tivities were systematically evaluated using a Caco-2 cell oxidative stress model.The results showed that supplementation with Limnospira platensis promoted a metabolic shift of carotenoids toward astaxanthin biosynthesis in Xanthophyllomyces dendrorhous,thereby increasing astaxanthin accumulation from 0.88±0.08 mg/g to 1.03±0.07 mg/g.Moreover,the two astaxanthin-loaded nanoparticles exhibited distinct physico-chemical properties and delivery behaviors,and their antioxidant effects were mainly achieved through scav-enging excessive intracellular reactive oxygen species.By integrating production enhancement with functional delivery,this study effectively improved the yield,stability,and bioavailability of astaxanthin.These findings provide further support for its potential applications in functional foods and nutraceutical delivery systems.展开更多
GABA(Gamma-aminobutyric acid),a crucial neurotransmitter in the central nervous system,has gained significant attention in recent years due to its extensive benefits for human health.The review focused on recent advan...GABA(Gamma-aminobutyric acid),a crucial neurotransmitter in the central nervous system,has gained significant attention in recent years due to its extensive benefits for human health.The review focused on recent advances in the biosynthesis and production of GABA.To begin with,the investigation evaluates GABA-producing strains and metabolic pathways,focusing on microbial sources such as Lactic Acid Bacteria,Escherichia coli,and Corynebac-terium glutamicum.The metabolic pathways of GABA are elaborated upon,including the GABA shunt and critical enzymes involved in its synthesis.Next,strategies to enhance microbial GABA production are discussed,including optimization of fermentation factors,different fermentation methods such as co-culture strategy and two-step fermentation,and modification of the GABA metabolic pathway.The review also explores methods for determining glutamate(Glu)and GABA levels,emphasizing the importance of accurate quantification.Furthermore,a comprehensive market analysis and prospects are provided,highlighting current trends,potential applications,and challenges in the GABA industry.Overall,this review serves as a valuable resource for researchers and industrialists working on GABA advancements,focusing on its efficient synthesis processes and various applications,and providing novel ideas and approaches to improve GABA yield and quality.展开更多
The marine algal-derived endophytic fungus Aspergillus wentii EN-48 produces the potential anti-tumor agent asperolide A, a tetranorlabdane diterpenoid active against lung cancer. However, the fermentation yield of as...The marine algal-derived endophytic fungus Aspergillus wentii EN-48 produces the potential anti-tumor agent asperolide A, a tetranorlabdane diterpenoid active against lung cancer. However, the fermentation yield of asperolide A was very low and only produced in static cultures. Static fermentation conditions of A. wentii EN-48 were optimized employing response surface methodology to enhance the production of asperolide A. The optimized conditions resulted in a 13.9-fold yield enhancement, which matched the predicted value, and the optimized conditions were successfully used in scale-up fermentation for the production of asperolide A. Exogenous addition of plant hormones （especially 10 pmol/L methyl jasmonate） stimulated asperolide A production. To our knowledge, this is first optimized production of an asperolide by a marine-derived fungus. The optimization is effective and valuable to supply material for further anti-tumor mechanism studies and preclinical evaluation of asperolide A and other norditerpenoids.展开更多
The present study deals with the kinetics of improved poly(3-hydroxybutyrate)(PHB)production by an L-cysteine HCl-depressed mutant of Bacillus licheniformis.Production of biodegradable polymers is to eliminate use of ...The present study deals with the kinetics of improved poly(3-hydroxybutyrate)(PHB)production by an L-cysteine HCl-depressed mutant of Bacillus licheniformis.Production of biodegradable polymers is to eliminate use of materials derived from petrochemicals and also because of their environmental impact.For the current study,mutant strain(NA-21)&wild-type(IIB-isl19)were used for PHB production.Submerged culture with two-stage fermentation technique was used for PHB production.Results indicated that PHB production was improved with 300 mM of-HNO2.The superior mutant strain(NA-21)resulted in 2-fold more PHB as compared to the wild-type(IIB-isl9).It was selected,and resistance against L-cysteine HCl was developed.At 4 ppm concentration of L-cysteine HCl,PHB production by mutant strain(NA-cys4)was higher than its wild counterpart by 5.7-fold.Kinetic study of parameters including specific growth rate(μh−1),growth(Yx/s,Ys/x),product yield coefficients(Yp/s,Yp/x),volumetric rate constants(Qp,Qs,Qx)and specific rate constants(qp,qs,qx),were also accomplished.Moreover,Yp/x,Qp and qp=μ×Yp/x were found to be very significant as 1.254±0.06(g/g biomass),0.134±0.01(g/l/h)and 0.168±0.01(g/g/h),respectively.The effect of fatty acids on PHB production highlighted the improvement in PHB production by 1.94-fold.The highest PHB production during the study was 16.35±3.12 g/l which highlighted its significance(p≤0.05)and impact on the overall process.The variation in PBH yield between wild-type and mutant B.licheniformis is possibly because of induced DNA interstrand thus making unstable thymidine-thymidine dymers.From the results,it was concluded that improved PHB production on industrial scale is fairly possible and it holds the potential to contribute significantly to plastic circularity in the future.展开更多
Gentamicin,an aminoglycoside antibiotic,is generated by a few species within the genus Micromonospora and has garnered significant attention due to its broad-spectrum efficacy in combating numerous infectious diseases...Gentamicin,an aminoglycoside antibiotic,is generated by a few species within the genus Micromonospora and has garnered significant attention due to its broad-spectrum efficacy in combating numerous infectious diseases.Comprising a complex array of closely related aminoglycoside compounds,the gentamicin B and C complexes emerge as particularly pertinent in clinical contexts.This review outlines the latest advancements in the biosynthesis and production of gentamicin,commencing with a comprehensive overview of its biosynthetic pathway.Subsequently,the article encapsulates a spectrum of strategies currently deployed to augment genta-micin yields.These strategies include mutation screening,molecular biological techniques,and optimization of the fermentation process.Moreover,numerous methods have been documented for detecting gentamicin across a range of matrices,underscoring the significance of precise quantitative analysis.Finally,the review furnishes an exhaustive market analysis and future outlook,elucidating prevailing trends and challenges within the genta-micin industry.Overall,this article serves as a pivotal resource for researchers and professionals engaged in gentamicin research,furnishing a meticulous introduction to efficient synthesis technologies and diverse ap-plications,alongside presenting innovative concepts and methodologies aimed at increasing gentamicin production.展开更多
The biosynthesis of bioactive secondary metabolites,specifically antibiotics,is of great scientific and economic importance.The control of antibiotic production typically involves different processes and molecular mec...The biosynthesis of bioactive secondary metabolites,specifically antibiotics,is of great scientific and economic importance.The control of antibiotic production typically involves different processes and molecular mechanism.Despite numerous efforts to improve antibiotic yields,joint engineering strategies for combining genetic manipulation with fermentation optimization remain finite.Lincomycin A(Lin-A),a lincosamide antibiotic,is industrially fermented by Streptomyces lincolnensis.Herein,the leucine-responsive regulatory protein(Lrp)-type regulator SLCG_4846 was confirmed to directly inhibit the lincomycin biosynthesis,whereas indirectly controlled the transcription of SLCG_2919,the first reported repressor in S.lincolnensis.Inactivation of SLCG_4846 in the high-yield S.lincolnensis LA219X(LA219XΔ4846)increases the Lin-A production and deletion of SLCG_2919 in LA219XΔ4846 exhibits superimposed yield increment.Given the effect of the double deletion on cellular primary metabolism of S.lincolnensis,Plackett-Burman design,steepest ascent and response surface methodologies were utilized and employed to optimize the seed medium of this double mutant in shake flask,and Lin-A yield using optimal seed medium was significantly increased over the control.Above strategies were performed in a 15-L fermenter.The maximal yield of Lin-A in LA219XΔ4846-2919 reached 6.56 g/L at 216 h,55.1%higher than that in LA219X at the parental cultivation(4.23 g/L).This study not only showcases the potential of this strategy to boost lincomycin production,but also could empower the development of high-performance actinomycetes for other antibiotics.展开更多
基金Projects(50621063, 50674101) supported by the National Natural Science Foundation of China
文摘In order to solve the citrus peel resource waste problem protopectinase-overproducing strain CD-01 for pectin production and minimize the drawbacks of chemical extraction of pectin, a was isolated from a pit soil dumped with perished orange in Changde City, Hunan Province of China. The strain CD-01 had the same morphology and 28S rRNA gene sequence （FJ184995） as that of Aspergillus niger （ATCC 64028）. It was thus identified and named as Aspergillus niger CD-01. The fermentation condition was optimized based on L9（34） orthogonal experimental design and the variances analyses. The results show that the optimal condition for producing pectin is as follows： time 36 h, temperature 35 ℃, pH 5, and urea as the nitrogen source. Under this condition, the pectin yield can reach up to 24.5%. This shows a great potential of Aspergillus niger CD-01 in pectin extraction from citrus.
基金Supported by the Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDC 0110300The Youth Project of Hebei Province Natural Science Foundation(C20211407039).
文摘The global demand for large-scale and cost-effective production of high-quality protein has become increasingly urgent,with microbial protein derived from methanol being recognized as a promising solution.Among 50 methylotrophic strains,Methylophilus sp.HN238 was selected for its capability to utilize methanol as the sole carbon.Through optimization of the medium composition,a 387.30%increase in protein yield was achieved during shake-flask fermentation.Subsequent scale-up to a 5 L bioreactor resulted in a protein content of 57.30%.Amino acid composition analysis revealed that 18 amino acids were quantitatively detectable in the protein,with essential amino acids accounting for 44.10%of the total composition,thereby demonstrating compliance with the World Health Organization(WHO)standards for high-quality protein.Tran-scriptomic differential analysis was conducted to investigate the metabolic response of Methylophilus sp.HN238 to methanol concentrations(10 g/L vs.50 g/L).It was observed that high methanol concentrations promoted the upregulation of methanol dehydrogenase(MDH)encoded by the maxI gene,while formaldehyde dehydrogenase(FLD)and cytochrome c(cyt c)were downregulated.This regulatory imbalance was associated with intracellular formaldehyde accumulation,impaired electron transport chain efficiency,oxidative stress,and subsequent inhibition of cellular growth.The study not only validated the potential of Methylophilus sp.HN238 for protein production with high methanol concentrations but also provided critical insights into metabolic engineering strategies to enhance methanol-to-biomass conversion efficiency.
基金supported by the National Natural Science Foundation project(grant number 32170057).
文摘Fidaxomicin,a macrolide antibiotic,is widely used to treat Clostridioides difficile infection(CDI).It demonstrats significantly higher clinical efficacy than vancomycin and metronidazole.However,the large-scale industrial production of it remains a significant challenge because of the low fermentation yields.In this study,we chosen the strain OE-R1/WT as the starting strain,in which a pathway-specific positive regulatory factor fadR1 was overexpressed.By using the kanR/gusA dual-reporter system and ARTP mutagenesis,we screened a high-yield strain,PA-13,which produced 757.34 mg/L of fidaxomicin,representing a 5.5-fold increase over OE-R1/WT and having enhanced genetic stability.Furthermore,by overexpressing two methyltransferases within the biosynthetic cluster and supplementing with exogenous DMSO,we further increased the production of fidax-omicin to 929.17 mg/L,while reducing the accumulation of the major by-product to 20.9%.Finally,through the optimization of fermentation strategies at both the shake flask and 15 L fermenter levels,we achieved a final yield of 3949.05 mg/L in the 15 L fermenter,which represents the highest yield up to date.Our study represents the first successful enhancement of fidaxomicin production in Actinoplanes deccanensis to over 3.9 g/L in a 15 L fermenter,establishing a robust foundation for industrial-scale fermentation.Additionally,it provides significant insights for the development of high-yield strains in other actinomycetes.
基金Supported by the Science Technology Development Project of Jilin Province,China(No.20020503-2)
文摘A sequential statistical approach was applied to optimizing the fermentation medium of epothilones（Epos） production by means of a mutant which was obtained by treating polyangium cellulosum ATCC 15384 with nitrite and ultraviolet. The effects of different carbon sources and nitrogen sources on the fermentation medium were tested, and the suitable ones were selected. Then a uniform design was employed to design the experiments. A linear model was developed for identifying the significant components in fermentation medium, while a third degree polynomial model was used for studying the relationship between the concentration of the components in fermentation medium and the yield of Epos（YEPs）. A pattern search method was used for searching the optimum fermentation medium in the test space, which was as follows（g/L）： potassium nitrate 8.00, soybean peptone 17.60, potassium hydrogen phos- phate 1.00, beef extraction 6.46, yeast extraction 1.00, calcium chloride 0.25, sodium chloride 1.00 and ferric chloride 0.02. The optimum fermentation medium was expected to result in a yield of Epos（YEPs） of 2.48 mg/L. The validation experiments with the optimum medium were performed in triplicate and the average yield of Epos was 2.45 mg/L which was 7.78 times higher than that of Epos prepared without optimization.
基金Supported by the National Natural Science Foundation of China(21276111,21206053,61305017)the Programme of Introducing Talents of Discipline to Universities(B12018)+2 种基金Fundamental Research Funds for the Central Universities(JUSRP11558)the Natural Science Foundation of Jiangsu Province(no.BK20160162)the Fundamental Research Funds for the Central Universities(JUSRP51510)
文摘Chinese rice wine making is a typical simultaneous saccharification and fermentation （SSF） process. During the fermentation process, temperature is one of the key parameters which decide the quality of Chinese rice wine. To optimize the SSF process for Chinese rice wine brewing, the effects of temperature on the kinetic parameters of yeast growth and ethanol production at various temperatures were determined in batch cultures using a mathematical model. The kinetic parameters as a function of temperature were evaluated using the software Origin8.0. Combing these functions with the mathematical model, an appropriate form of the model equations for the SSF considering the effects of temperature were developed. The kinetic parameters were found to fit the experimental data satisfactorily with the developed temperature-dependent model. The temperature profile for maximizing the ethanol production for rice wine fermentation was determined by genetic algorithm. The optimum temperature profile began at a low temperature of 26℃ up to 30 h. The operating temperature increased rapidly to 31.9 ℃, and then decreased slowly to 18℃ at 65 h. Thereafter, the temperature was maintained at 18 ℃ until the end of fermentation. A maximum ethanol production of 89.3 g.L 1 was attained. Conceivably, our model would facilitate the improvement of Chinese rice wine production at the industrial scale.
基金Supported by the Research Project of Science and Technology of Zhejiang Province, China （2005C23027）, the National High Technology Research and Development Program of China （2007AA021506） and the Natural Science Foundation of Zhejiang Province （R207609）. We would like to thank Dr. Birnie from New Zealand for his editing of this manuscript.
文摘A strain isolated from the fruiting body of a fungus parasitized on Elaphomyces was identified as Cordyceps ophioglossoides based on the morphological characteristics and the analysis of ITS-5.8s rDNA sequence. The optimal medium, composition （g·L^-1）, containing sucrose 66.0, yeast powder 10.0, silkworm chrysalises digest 30.0, MgSO4· 7H2O 0.4, and KH2PO4 0.4, Was found using fractional factorial design ancl a central composite design, and the optimization of cultural conditions obtained a result of seed age 6 days, inoculum size 6% （by volume）, initial pH 5.6, temperature 24℃, shaking speed 160 ·＇min^-1 by one-factor-at-a-time method. The maximum biomass reached about 20.2 g·L^-1 after 90 hours culture under the optimal conditions. Elementary nharmaeclogical actlwtties showed that mycelia of C. ophioglossoides L2 from submerged culture promoted Uterus growth in estrogen- depleted mice. In the 15-litre scale-up fermentation, the mycelial biomass was around 19.1 g·L^-1, indicating a promising prospect for this biotechnoloagy and the potency to develoo its medical value.
基金Supported by Research Project of Sichuan University of Science&Engineering(No.2011RC12,2014KY02)Scientific Research Foundation of the Education Department of Sichuan Province(No.15ZA0222)Research Project of Liquor-marking Biological Technology and Application of Key Laboratory of Sichuan Province(NJ2013-06)
文摘[Objective]This study aimed to improve the yield of bacteriocins from lactic acid bacteria by optimizing the fermentation process for production of bacteriocins from lactic acid bacteria.[Method]By single-factor analysis,fermentation temperature,seed age,inoculation volume,fermentation duration and fermentation media p H were optimized to determine the best fermentation process.The inhibitory zone of bacteriocins from lactic acid bacteria was analyzed with oxford cup method,based on which the fermentation process was evaluated.[Result]The optimal fermentation process was optimized：fermentation temperature 37℃,seed age 14 h,inoculation volume 2%,fermentation duration 48 h,fermentation media p H 5.0.[Conclusion]Under the optimized fermentation conditions,the yield of bacteriocins from lactic acid bacteria was improved significantly.
基金supported by the National Natural Science Foundation of China(Nos.31201557 and 31270155)the Natural Science Foundation of Shanghai(No.12ZR1414100)+2 种基金the Foundation of Basic Science and Technology of China(No.2014FY20900)the Ministry of Education University Doctoral Foundation(No.20120073120070)the Shanghai Jiao Tong University Medical-Engineering Cross Research Fund(No.YG2015MS37),China
文摘Trichoderma-based formulations are applied as commercial biocontrol agents for soil-borne plant path- ogens. Chlamydospores are active propagules in Trichoderma spp., but their production is currently limited due to a lack of optimal liquid fermentation technology. In this study, we explored response surface methodologies for opti- mizing fermentation technology in Trichoderma SH2303. Our initial studies, using the Plackett-Burman design, iden- tified cornmeal, glycerol, and initial pH levels as the most significant factors （P〈0.05） for enhancing the production of chlamydospores. Subsequently, we applied the Box-Behnken design to study the interactions between, and optimal levels of, a number of factors in chlamydospore production. These statistically predicted results indicated that the highest number of chlamydospores （3.6×108 spores/ml） would be obtained under the following condition： corn flour 62.86 g/L, glycerol 7.54 ml/L, pH 4.17, and 6-d incubation in liquid fermentation. We validated these predicted values via three repeated experiments using the optimal culture and achieved maximum chlamydospores of 4.5×108 spores/ml, which approximately a 8-fold increase in the number of chlamydospores produced by T. harzianurn SH2303 compared with that before optimization. These optimized values could help make chlamydospore production cost-efficient in the future development of novel biocontrol agents.
基金supported by the Major Program of the Hebei Province Commission of Science and Technology during the 11 th Five-Year-Plan period,China(06220106D)
文摘Strain of Pseudomonas Lip35 producing lipase was isolated in a refrigerator. Lipase production and characterization of this strain were investigated under different conditions. The Pseudomonas was cultivated in shaking flasks in a fermentation medium in various nutritional and physical environments. Lipase production has been influenced by the presence of yeast-extract, soybean powder, NaCI, and Tween-80. Maximum lipase productivity was obtained when the physical environment of the fermentation medium was optimal for 67 h. The production of lipase reached 58.9 U·mL^-1. The lipase of Pseudomonas Lip35 can be considered to be inducible, but the inducer had little influence on the production of lipase. The lipase was characterized and showed high lipolytic activity from pH 7.5-8.0. The optimum temperature was observed at 20℃ and the thermal inactivation of lipase was obvious at 60℃. The lipase activity was inhibited by K＋, stimulated by Ca^2＋, and thermostability decreased in the presence of Ca^2＋, therefore the lipase was Ca^2＋ -dependent cold-adapted enzyme.
基金Supported by the National Basic Research Program of China(2013CB733600)the Key Program of National Natural Science Foundation of China(21236005)+1 种基金the Natural Science Foundation of Tianjin(12JCZDJC21900)the Program of Introducing Talents of Discipline to Universities(B06006)
文摘Foaming reduces the working volume and limits the biosynthesis of macrolide immunosuppressant ascomycin(FK520) in the batch fermentation process of Streptomyces hygroscopicus FS-35 in a 7.5 L bioreactor. To find the relation between FK520 production and foaming, effects of 10 fermentation parameters including organic acids and membrane permeability were investigated. The results suggest that acetate accumulation caused by short period oxygen de ficiency and fast consumption of glucose is the reason for increased foaming and declined FK520 production. Therefore, a fed-batch fermentation strategy was developed to reduce the accumulation of acetate. After optimization, the maximum acetate concentration dropped from 320 mg·L-1to 157 mg·L-1, decreased by 50.8%, and the maximum foam height reduced from 5.32 cm to 3.74 cm, decreased by 29.7%, while the maximum FK520 production increased from 375 mg·L-1to 421 mg·L-1, improved by 12%.
文摘The soybean cultivar Tadang Muangpai was used to improve the productive quality of Thua-Nao and reduce the concentration of aflatoxin to less than 20 ppb. It was conducted at CMFCRC, Chiangmai, Thailand between Dec. 2006 and Mar. 2007. Soybean was boiled for 5 hours and then fermented at different time to create natural bacterial species, mainly Bacillus spp. Thua-Nao could be stored up to 90 days after in storage. Nutritional value, food value, and microorganisms content were investigated during fermentation and storage. Also, aflatoxin content of Thua-Nao was recorded during storage. The results showed that 3 days of soybean fermentation gave the best performance of Thua-Nao in term of nutritional value （protein = 47.12%）, food value, and content of Bacillus spp. （2.78 × 10^9 CFU/g）. Without being harmed from aflatoxin, Thua-Nao could be stored not more than 23 days in normal room （Tmax. = 33.9 ℃, Tmin. = 15.8 ℃） and not more than 36 days in climate-controlled room （Tmax. = 20 ℃, Tmin. = 15 ℃）.
文摘This study explores the multifaceted regulatory mechanisms of Thermophilic actinomycetes MC-34(TA)in solidstate fermentation of Chinese Baijiu,focusing on their synergistic enhancement of flavor quality.Through monoand co-culture fermentation experiments,we revealed that the introduction of thermophilic TA significantly enhances ethanol production(up to 269.56%increase)and sugar-alcohol conversion efficiency(up to 164.41%increase).The activation of interspecies metabolic interaction networks via hydrolase secretion promotes the biosynthesis of 23 characteristic flavor compounds(e.g.,ethyl acetate and isoamyl alcohol),resulting in 20%-30%greater flavor diversity in experimental groups compared to controls.First,TA were found to enrich organic acid profiles(e.g.,isobutyric acid)via cooperative metabolic pathways,concurrently stabilizing environmental pH(50%reduction in pH fluctuation during the late fermentation phase).Furthermore,a novel mechanism was identified:TA inhibitedα-amylase and glucoamylase activities(maximum inhibition rate:98.9%),thereby optimizing substrate utilization efficiency through enzymatic balance regulation.This study challenges the conventional view that TA only participates in terpenoid synthesis.Instead,it innovatively constructs a synergistic metabolic network model involving actinomycetes,yeast,and mold.These findings provide theoretical foundations for synthetic microbial consortia development and modernization of traditional brewing processes,offering critical references for enhancing Baijiu flavor quality and industrial production optimization.
文摘Stevia rebaudiana was incorporated into kombucha fermentation to evaluate its effects on fermentation dynamics and metabolite production.Fermentation conditions were optimized using response surface methodology and validated with an electronic tongue system.Volatile compounds in kombucha samples with and without Stevia rebaudiana were characterized via gas chromatography-mass spectrometry(GC-MS).Metagenomic analysis identified Komagataeibacter,Brettanomyces,and Gluconobacter as the dominant genera in both sample types,and their correlations with volatile compounds were visualized through heatmap analysis.Untargeted metabolomics revealed the formation and transformation of key metabolites throughout fermentation,providing insights into changes in total phenolic and flavonoid contents.These findings offer a mechanistic understanding of how Stevia rebaudiana modulates kombucha fermentation,flavor development,and bioactive compound production.
基金Indian Council of Agricultural Research,New Delhi for funding under“Genome Editing Project”(ICAR/GR-1/2326).
文摘Sugar polyols,including xylitol,erythritol,mannitol and sorbitol are vital nutritional sweeteners having significant applications across various sectors like food,pharmaceuticals,and cosmetics.Metabolic engineering in microbes is a center of attraction to produce value-added products from the lignocellulosic biomass.Clustered regularly interspaced short palindromic repeats(CRISPR)/Cas9 has emerged as a powerful and transformative platform in molecular biology,offering innovative solutions for enhancing the biosynthesis of sugar polyols,paving the way for more efficient and cost-effective production methods.This review aims to offer a thorough overview of CRISPR/Cas9 technology and its role in enhancing production of sugar polyols in microbial systems.It focuses on recent advancements and optimization strategies for improving polyol biosynthesis and productivity through CRISPR/Cas9 based gene editing and fermentation process optimization.The review highlights several successful implementations of CRISPR/Cas9 technology in modifying biosynthetic pathways for sugar polyol production in microbes.Continued research and development in this area are likely to lead to further improvements in efficiency and scalability,benefiting various industries particularly food and pharmaceutical industry that rely on these valuable compounds.
基金funded through National Promotion Project of Scientific and Technological Achievements in Forestry and Grassland(2020133135)the China Agriculture Research System of MOF and MARA(CARS-21).
文摘Astaxanthin,as a natural keto-carotenoid,demonstrates remarkable antioxidant properties.However,the naturally occurring trans-structured free astaxanthin is limited by restricted natural availability and low in-dustrial production yield.Furthermore,its molecular architecture rich in unsaturated double bonds and inherent hydrophobicity critically undermines its stability and bioavailability.In this study,an integrated strategy spanning from production enhancement to functional delivery was established.Xanthophyllomyces dendrorhous,a red yeast,was used to ferment Limnospira platensis,with fermentation parameters systematically optimized to promote astaxanthin accumulation.Subsequently,astaxanthin produced from the optimized fermentation pro-cess was extracted and formulated into two types of astaxanthin-loaded nanoparticles,whose antioxidant ac-tivities were systematically evaluated using a Caco-2 cell oxidative stress model.The results showed that supplementation with Limnospira platensis promoted a metabolic shift of carotenoids toward astaxanthin biosynthesis in Xanthophyllomyces dendrorhous,thereby increasing astaxanthin accumulation from 0.88±0.08 mg/g to 1.03±0.07 mg/g.Moreover,the two astaxanthin-loaded nanoparticles exhibited distinct physico-chemical properties and delivery behaviors,and their antioxidant effects were mainly achieved through scav-enging excessive intracellular reactive oxygen species.By integrating production enhancement with functional delivery,this study effectively improved the yield,stability,and bioavailability of astaxanthin.These findings provide further support for its potential applications in functional foods and nutraceutical delivery systems.
基金financially supported by the National Key Research and Development Program of China(No.2019YFA0905700)the Natural Science Foundation of Jiangsu Province(BK20211535)+2 种基金Jiangsu agricultral science and technology innovation fund(CX233055)the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture(XTD2213)Jiangsu Province“333”project(2022).
文摘GABA(Gamma-aminobutyric acid),a crucial neurotransmitter in the central nervous system,has gained significant attention in recent years due to its extensive benefits for human health.The review focused on recent advances in the biosynthesis and production of GABA.To begin with,the investigation evaluates GABA-producing strains and metabolic pathways,focusing on microbial sources such as Lactic Acid Bacteria,Escherichia coli,and Corynebac-terium glutamicum.The metabolic pathways of GABA are elaborated upon,including the GABA shunt and critical enzymes involved in its synthesis.Next,strategies to enhance microbial GABA production are discussed,including optimization of fermentation factors,different fermentation methods such as co-culture strategy and two-step fermentation,and modification of the GABA metabolic pathway.The review also explores methods for determining glutamate(Glu)and GABA levels,emphasizing the importance of accurate quantification.Furthermore,a comprehensive market analysis and prospects are provided,highlighting current trends,potential applications,and challenges in the GABA industry.Overall,this review serves as a valuable resource for researchers and industrialists working on GABA advancements,focusing on its efficient synthesis processes and various applications,and providing novel ideas and approaches to improve GABA yield and quality.
基金Supported by the National Natural Science Foundation of China(NSFC,Nos.31200042,31570038)the NSFC-Shandong Joint Fund for Marine Science Research Centers(No.U1406402)
文摘The marine algal-derived endophytic fungus Aspergillus wentii EN-48 produces the potential anti-tumor agent asperolide A, a tetranorlabdane diterpenoid active against lung cancer. However, the fermentation yield of asperolide A was very low and only produced in static cultures. Static fermentation conditions of A. wentii EN-48 were optimized employing response surface methodology to enhance the production of asperolide A. The optimized conditions resulted in a 13.9-fold yield enhancement, which matched the predicted value, and the optimized conditions were successfully used in scale-up fermentation for the production of asperolide A. Exogenous addition of plant hormones （especially 10 pmol/L methyl jasmonate） stimulated asperolide A production. To our knowledge, this is first optimized production of an asperolide by a marine-derived fungus. The optimization is effective and valuable to supply material for further anti-tumor mechanism studies and preclinical evaluation of asperolide A and other norditerpenoids.
基金the Researchers Supporting Project,King Saud University,Riyadh,Saudi Arabia for funding this work through the project number(RSP-2024R437).
文摘The present study deals with the kinetics of improved poly(3-hydroxybutyrate)(PHB)production by an L-cysteine HCl-depressed mutant of Bacillus licheniformis.Production of biodegradable polymers is to eliminate use of materials derived from petrochemicals and also because of their environmental impact.For the current study,mutant strain(NA-21)&wild-type(IIB-isl19)were used for PHB production.Submerged culture with two-stage fermentation technique was used for PHB production.Results indicated that PHB production was improved with 300 mM of-HNO2.The superior mutant strain(NA-21)resulted in 2-fold more PHB as compared to the wild-type(IIB-isl9).It was selected,and resistance against L-cysteine HCl was developed.At 4 ppm concentration of L-cysteine HCl,PHB production by mutant strain(NA-cys4)was higher than its wild counterpart by 5.7-fold.Kinetic study of parameters including specific growth rate(μh−1),growth(Yx/s,Ys/x),product yield coefficients(Yp/s,Yp/x),volumetric rate constants(Qp,Qs,Qx)and specific rate constants(qp,qs,qx),were also accomplished.Moreover,Yp/x,Qp and qp=μ×Yp/x were found to be very significant as 1.254±0.06(g/g biomass),0.134±0.01(g/l/h)and 0.168±0.01(g/g/h),respectively.The effect of fatty acids on PHB production highlighted the improvement in PHB production by 1.94-fold.The highest PHB production during the study was 16.35±3.12 g/l which highlighted its significance(p≤0.05)and impact on the overall process.The variation in PBH yield between wild-type and mutant B.licheniformis is possibly because of induced DNA interstrand thus making unstable thymidine-thymidine dymers.From the results,it was concluded that improved PHB production on industrial scale is fairly possible and it holds the potential to contribute significantly to plastic circularity in the future.
基金supported by the National Key Research and Development Program of China(2022YFC2105403)the Taishan Scholars Program+2 种基金the Shanghai Pilot Program for Basic Research(22TQ1400100-14)the Natural Science Foundation of Shanghai(23ZR1416500)the Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVJ1231036)。
文摘Gentamicin,an aminoglycoside antibiotic,is generated by a few species within the genus Micromonospora and has garnered significant attention due to its broad-spectrum efficacy in combating numerous infectious diseases.Comprising a complex array of closely related aminoglycoside compounds,the gentamicin B and C complexes emerge as particularly pertinent in clinical contexts.This review outlines the latest advancements in the biosynthesis and production of gentamicin,commencing with a comprehensive overview of its biosynthetic pathway.Subsequently,the article encapsulates a spectrum of strategies currently deployed to augment genta-micin yields.These strategies include mutation screening,molecular biological techniques,and optimization of the fermentation process.Moreover,numerous methods have been documented for detecting gentamicin across a range of matrices,underscoring the significance of precise quantitative analysis.Finally,the review furnishes an exhaustive market analysis and future outlook,elucidating prevailing trends and challenges within the genta-micin industry.Overall,this article serves as a pivotal resource for researchers and professionals engaged in gentamicin research,furnishing a meticulous introduction to efficient synthesis technologies and diverse ap-plications,alongside presenting innovative concepts and methodologies aimed at increasing gentamicin production.
基金supported in part by the Anhui Provincial Natural Science Foundation for Excellent Young Scholars(grant no.2208085Y09)the National Natural Science Foundation of China(grant no.32170073,31972930).
文摘The biosynthesis of bioactive secondary metabolites,specifically antibiotics,is of great scientific and economic importance.The control of antibiotic production typically involves different processes and molecular mechanism.Despite numerous efforts to improve antibiotic yields,joint engineering strategies for combining genetic manipulation with fermentation optimization remain finite.Lincomycin A(Lin-A),a lincosamide antibiotic,is industrially fermented by Streptomyces lincolnensis.Herein,the leucine-responsive regulatory protein(Lrp)-type regulator SLCG_4846 was confirmed to directly inhibit the lincomycin biosynthesis,whereas indirectly controlled the transcription of SLCG_2919,the first reported repressor in S.lincolnensis.Inactivation of SLCG_4846 in the high-yield S.lincolnensis LA219X(LA219XΔ4846)increases the Lin-A production and deletion of SLCG_2919 in LA219XΔ4846 exhibits superimposed yield increment.Given the effect of the double deletion on cellular primary metabolism of S.lincolnensis,Plackett-Burman design,steepest ascent and response surface methodologies were utilized and employed to optimize the seed medium of this double mutant in shake flask,and Lin-A yield using optimal seed medium was significantly increased over the control.Above strategies were performed in a 15-L fermenter.The maximal yield of Lin-A in LA219XΔ4846-2919 reached 6.56 g/L at 216 h,55.1%higher than that in LA219X at the parental cultivation(4.23 g/L).This study not only showcases the potential of this strategy to boost lincomycin production,but also could empower the development of high-performance actinomycetes for other antibiotics.
