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
Ergothioneine,a rare sulfur-containing amino acid with potent antioxidant and cytoprotective activities,holds significant promise in pharmaceutical and nutraceutical applications,necessitating the development of effic...Ergothioneine,a rare sulfur-containing amino acid with potent antioxidant and cytoprotective activities,holds significant promise in pharmaceutical and nutraceutical applications,necessitating the development of efficient and sustainable production methods.This study leveraged the GRAS(Generally Recognized as Safe)yeast Kluyveromyces lactis as a novel chassis for de novo biosynthesis of EGT.First,the ergothioneine synthase genes ShEgt1-ShEgt2 from Stereum hirsutum were heterologously expressed and integrated into the K.lactis genome,yielding the engineered strain KL2 EGT28.Subsequently,metabolic pathway engineering focused on improving the supply of key precursors(histidine,cysteine,methionine),alongside fermentation condition optimization.Shake flask experiments with an optimized medium containing 20 g/L glucose,4 g/L histidine,and 10 g/L methionine increased EGT titer to 188.17±0.44 mg/L.In a 5 L fermenter,a refined fed-batch strategy(maintaining 5-10 g/L residual glucose,pH 7.0)further boosted production to 398.64±0.21 mg/L within 96 h,representing an 18-fold improvement over initial constructs.This study provides a foundational strategy for costeffective biomanufacturing of high-value compounds using non-conventional yeast chassis.展开更多
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 by the National Key Research and Development Program of China(2023YFF1103400)the Jiangsu Basic Research Center for Synthetic Biology(No.BK20233003).
文摘Ergothioneine,a rare sulfur-containing amino acid with potent antioxidant and cytoprotective activities,holds significant promise in pharmaceutical and nutraceutical applications,necessitating the development of efficient and sustainable production methods.This study leveraged the GRAS(Generally Recognized as Safe)yeast Kluyveromyces lactis as a novel chassis for de novo biosynthesis of EGT.First,the ergothioneine synthase genes ShEgt1-ShEgt2 from Stereum hirsutum were heterologously expressed and integrated into the K.lactis genome,yielding the engineered strain KL2 EGT28.Subsequently,metabolic pathway engineering focused on improving the supply of key precursors(histidine,cysteine,methionine),alongside fermentation condition optimization.Shake flask experiments with an optimized medium containing 20 g/L glucose,4 g/L histidine,and 10 g/L methionine increased EGT titer to 188.17±0.44 mg/L.In a 5 L fermenter,a refined fed-batch strategy(maintaining 5-10 g/L residual glucose,pH 7.0)further boosted production to 398.64±0.21 mg/L within 96 h,representing an 18-fold improvement over initial constructs.This study provides a foundational strategy for costeffective biomanufacturing of high-value compounds using non-conventional yeast chassis.
