Synthetic and Systems Biotechnology最新文献_第10页

Enhancing abscisic acid production in Botrytis cinerea through metabolic engineering based on a constitutive promoter library 基于组成启动子文库的代谢工程提高灰葡萄孢脱落酸产量。

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-12-20 DOI: 10.1016/j.synbio.2024.12.004

Ling-Ru Wang , Ji-Zi-Hao Tang , Shu-Ting Zhu , Na Wu , Zhi-Kui Nie , Tian-Qiong Shi

{"title":"Enhancing abscisic acid production in Botrytis cinerea through metabolic engineering based on a constitutive promoter library","authors":"Ling-Ru Wang , Ji-Zi-Hao Tang , Shu-Ting Zhu , Na Wu , Zhi-Kui Nie , Tian-Qiong Shi","doi":"10.1016/j.synbio.2024.12.004","DOIUrl":"10.1016/j.synbio.2024.12.004","url":null,"abstract":"<div><div>Abscisic acid (ABA) is an important plant growth regulator with broad applications in agriculture, forestry, and other fields. Currently, the industrial production of ABA primarily relies on microbial fermentation using <em>Botrytis cinerea</em>, but its genetic toolbox is limited. To address this, we first screened 10 strong constitutive promoters from the genome of <em>B. cinerea</em> through transcriptomic analysis. The expression levels of the promoters covered a range of 3–4 orders of magnitude according to the measured β-glucuronidase activity. Subsequently, four promoters of different strength were used to balance the cofactor supply in <em>B. cinerea</em>. Overexpression of NADH kinase using the medium-strength promoter <em>Pef1a</em> significantly enhanced ABA production, resulting in a 32.26 % increase compared to the control. Finally, by combining promoter engineering with a push-pull strategy, we optimized the biosynthesis of ABA. The recombinant strain Pthi4:hmgr-Pef1a:a4, overexpressing HMGR under the <em>Pthi4</em> promoter and Bcaba4 under the <em>Pef1a</em> promoter, achieved an ABA titer of 1.18 g/L, a 58.92 % increase. To our best knowledge, this is the first constitutive promoter library suitable for <em>B. cinerea</em>, providing important tools for the industrial production of ABA.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 373-380"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling coding sequence design for virus-based expression in tobacco 为基于病毒的烟草表达设计编码序列模型。

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-12-11 DOI: 10.1016/j.synbio.2024.12.002

Moritz Burghardt , Tamir Tuller

{"title":"Modeling coding sequence design for virus-based expression in tobacco","authors":"Moritz Burghardt , Tamir Tuller","doi":"10.1016/j.synbio.2024.12.002","DOIUrl":"10.1016/j.synbio.2024.12.002","url":null,"abstract":"<div><div>Transient expression in Tobacco is a popular way to produce recombinant proteins in plants. The design of various expression vectors, delivered into the plant by <em>Agrobacterium</em>, has enabled high production levels of some proteins. To further enhance expression, researchers often adapt the coding sequence of heterologous genes to the host, but this strategy has produced mixed results in Tobacco.</div><div>To study the effects of different sequence features on protein yield, we compile a dataset of the yields and coding sequences of previously published expression studies of more than 200 coding sequences.</div><div>We evaluate various established gene expression models on a subset of the expression studies. We find that use of tobacco codons is only moderately predictive of protein yield as informative sequence features likely extend over multiple codons. Additionally, we show that codon usage of organisms that use tobacco as a host for expression of their proteins in a similar way as the synthetic system, like viruses and agrobacteria, can be used to predict heterologous expression. Other predictive features are related to tRNA supply and demand, the inclusion of a translational ramp of codons with lower adaptation to the tRNA pool at the beginning of the coding region, and the amino acid composition of the recombinant protein. A model based on all the features achieved a correlation of 0.57 with protein yield.</div><div>We believe that our study provides a practical guideline for coding sequence design for efficient expression in tobacco.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 337-345"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Construction of antibiotic-free riboflavin producer in Escherichia coli by metabolic engineering strategies with a plasmid stabilization system 利用质粒稳定系统的代谢工程策略构建大肠杆菌无抗生素核黄素生产体。

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-12-06 DOI: 10.1016/j.synbio.2024.12.001

Xiaoling Zhang , Yanan Li , Kang Wang , Jilong Yin , Yuxuan Du , Zhen Yang , Xuewei Pan , Jiajia You , Zhiming Rao

{"title":"Construction of antibiotic-free riboflavin producer in Escherichia coli by metabolic engineering strategies with a plasmid stabilization system","authors":"Xiaoling Zhang , Yanan Li , Kang Wang , Jilong Yin , Yuxuan Du , Zhen Yang , Xuewei Pan , Jiajia You , Zhiming Rao","doi":"10.1016/j.synbio.2024.12.001","DOIUrl":"10.1016/j.synbio.2024.12.001","url":null,"abstract":"<div><div>Riboflavin, an important vitamin utilized in pharmaceutical products and as a feed additive, is mainly produced by metabolically engineered bacterial fermentation. However, the reliance on antibiotics in the production process leads to increased costs and safety risks. To address these challenges, an antibiotic-free <em>Escherichia coli</em> riboflavin producer was constructed using metabolic engineering approaches coupled with a novel plasmid stabilization system. Initially, competitive pathways and feedback inhibition were attenuated to enhance the metabolic flux towards riboflavin. Key genes in the purine pathway were overexpressed to boost the availability of riboflavin precursors. Subsequently, a plasmid stabilization system based on toxin was screened and characterized, achieving a plasmid retention rate of 84.9% after 10 days of passaging. Finally, transcriptomic analysis at the genome-wide level revealed several rate-limiting genes, including <em>pgl</em>, <em>gnd</em>, and <em>yigB</em>, which were subsequently upregulated, leading to a 26% improvement in riboflavin production. With optimization of the culture medium, the final strain allowed the production of 11.5 g/L of riboflavin with a yield of 90.4 mg/g glucose in 5 L bioreactors without antibiotics. These strategies can be extended to other plasmid-based riboflavin derivative production systems.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 346-355"},"PeriodicalIF":4.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Semi-rational design and modification of phosphoketolase to improve the yield of tyrosol in Saccharomyces cerevisiae 半合理设计和修饰磷酸酮醇酶以提高酿酒酵母酪醇的产率

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-26 DOI: 10.1016/j.synbio.2024.11.007

Na Song , Huili Xia , Yaoru Xie , Shuaikang Guo , Rong Zhou , Lingling Shangguan , Kun Zhuang , Huiyan Zhang , Feiran An , Xueyun Zheng , Lan Yao , Shihui Yang , Xiong Chen , Jun Dai

{"title":"Semi-rational design and modification of phosphoketolase to improve the yield of tyrosol in Saccharomyces cerevisiae","authors":"Na Song , Huili Xia , Yaoru Xie , Shuaikang Guo , Rong Zhou , Lingling Shangguan , Kun Zhuang , Huiyan Zhang , Feiran An , Xueyun Zheng , Lan Yao , Shihui Yang , Xiong Chen , Jun Dai","doi":"10.1016/j.synbio.2024.11.007","DOIUrl":"10.1016/j.synbio.2024.11.007","url":null,"abstract":"<div><div>Tyrosol is an important component of pharmaceuticals, nutraceuticals, and cosmetics, and their biosynthetic pathways are currently a hot research topic. <span>d</span>-Erythrose 4-phosphate is a key precursor for the biosynthesis of tyrosol in <em>Saccharomyces cerevisiae</em>. Hence, the flux of <span>d</span>-Erythrose 4-phosphate determined the yield of tyrosol synthesis. In this study, we first obtained an <em>S. cerevisiae</em> strain S19 with a tyrosol yield of 247.66 mg/L by metabolic engineering strategy. To increase the production of <span>d</span>-Erythrose 4-phosphate, highly active phosphoketolase BA-C was obtained by bioinformatics combined with tyrosol yield assay. The key residue sites 183, 217, and 320 were obtained by molecular docking, kinetic simulation, and tyrosol yield verification. After mutation, the highly efficient phosphoketolase BA-C<sup>His320Met</sup> was obtained, with a 37.32 % increase in enzyme activity. The tyrosol production of strain S26 with BA-C<sup>His320Arg</sup> increased by 43.05 % than strain S25 with BA-C and increased by 151.19 % compared with the strain S19 without phosphoketolase in a 20 L fermenter. The mining and modification of phosphoketolase will provide strong support for the de novo synthesis of aromatic compounds.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 294-306"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin 枯草芽孢杆菌改善去硫代生物素和生物素生产的途径和蛋白质通道工程

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-22 DOI: 10.1016/j.synbio.2024.11.005

Yue Wu , Guang-Qing Du , Dong-Han Ma , Jin-Long Li , Huan Fang , Hui-Na Dong , Zhao-Xia Jin , Da-Wei Zhang

{"title":"Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin","authors":"Yue Wu , Guang-Qing Du , Dong-Han Ma , Jin-Long Li , Huan Fang , Hui-Na Dong , Zhao-Xia Jin , Da-Wei Zhang","doi":"10.1016/j.synbio.2024.11.005","DOIUrl":"10.1016/j.synbio.2024.11.005","url":null,"abstract":"<div><div>Biotin (vitamin B<sub>7</sub>) is a crucial cofactor for various metabolic processes and has significant applications in pharmaceuticals, cosmetics, and animal feed. <em>Bacillus subtilis</em>, a well-studied Gram-positive bacterium, presents a promising host for biotin production due to its Generally Recognized as Safe (GRAS) status, robust genetic tractability, and capacity for metabolite secretion. This study focuses on the metabolic engineering of <em>B</em>. <em>subtilis</em> to enhance biotin biosynthesis. Initially, the desthiobiotin (DTB) and biotin synthesis ability of different <em>B</em>. <em>subtilis</em> strains were evaluated to screen for suitable chassis cells. Subsequently, the titers of DTB and biotin were increased to 21.6 mg/L and 2.7 mg/L, respectively, by relieving the feedback repression of biotin synthesis and deleting the biotin uptake protein YhfU. Finally, through engineering the access tunnel to the active site of biotin synthase (BioB) for reactants and modulating its expression, the biotin titer was increased to 11.2 mg/L, marking an 1130-fold improvement compared to the wild-type strain. These findings provide novel strategies for enhancing the production of DTB and improving the conversion efficiency of DTB to biotin.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 307-313"},"PeriodicalIF":4.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology 利用微生物异质性促进合成生物学催化的生物合成

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-19 DOI: 10.1016/j.synbio.2024.11.004

Yanting Cao , Jianghua Li , Long Liu , Guocheng Du , Yanfeng Liu

{"title":"Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology","authors":"Yanting Cao , Jianghua Li , Long Liu , Guocheng Du , Yanfeng Liu","doi":"10.1016/j.synbio.2024.11.004","DOIUrl":"10.1016/j.synbio.2024.11.004","url":null,"abstract":"<div><div>Metabolic engineering-driven microbial cell factories have made great progress in the efficient bioproduction of biochemical and recombinant proteins. However, the low efficiency and robustness of microbial cell factories limit their industrial applications. Harnessing microbial heterogeneity contributes to solving this. In this review, the origins of microbial heterogeneity and its effects on biosynthesis are first summarized. Synthetic biology-driven tools and strategies that can be used to improve biosynthesis by increasing and reducing microbial heterogeneity are then systematically summarized. Next, novel single-cell technologies available for unraveling microbial heterogeneity and facilitating heterogeneity regulation are discussed. Furthermore, a combined workflow of increasing genetic heterogeneity in the strain-building step to help in screening highly productive strains - reducing heterogeneity in the production process to obtain highly robust strains (IHP-RHR) facilitated by single-cell technologies was proposed to obtain highly productive and robust strains by harnessing microbial heterogeneity. Finally, the prospects and future challenges are discussed.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 281-293"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advances in the biosynthesis and production optimization of gentamicin: A critical review 庆大霉素生物合成和生产优化的最新进展：重要综述

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-14 DOI: 10.1016/j.synbio.2024.11.003

Feng Xu, Kaihao Hu, Ali Mohsin, Jie Wu, Lihuan Su, Yuan Wang, Rong Ben, Hao Gao, Xiwei Tian, Ju Chu

{"title":"Recent advances in the biosynthesis and production optimization of gentamicin: A critical review","authors":"Feng Xu, Kaihao Hu, Ali Mohsin, Jie Wu, Lihuan Su, Yuan Wang, Rong Ben, Hao Gao, Xiwei Tian, Ju Chu","doi":"10.1016/j.synbio.2024.11.003","DOIUrl":"10.1016/j.synbio.2024.11.003","url":null,"abstract":"<div><div>Gentamicin, an aminoglycoside antibiotic, is generated by a few species within the genus <em>Micromonospora</em> 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 gentamicin 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 gentamicin 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 applications, alongside presenting innovative concepts and methodologies aimed at increasing gentamicin production.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 247-261"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coordinated regulation of two LacI family regulators, GvmR and GvmR2, on guvermectin production in Streptomyces caniferus 两种 LacI 家族调控因子 GvmR 和 GvmR2 对罐头链霉菌生产古维菌素的协调调控

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-09 DOI: 10.1016/j.synbio.2024.11.001

Haoran Shi , Jiabin Wang , Shanshan Li , Chongxi Liu , Lei Li , Zhuoxu Dong , Lan Ye , Xiangjing Wang , Yanyan Zhang , Wensheng Xiang

{"title":"Coordinated regulation of two LacI family regulators, GvmR and GvmR2, on guvermectin production in Streptomyces caniferus","authors":"Haoran Shi , Jiabin Wang , Shanshan Li , Chongxi Liu , Lei Li , Zhuoxu Dong , Lan Ye , Xiangjing Wang , Yanyan Zhang , Wensheng Xiang","doi":"10.1016/j.synbio.2024.11.001","DOIUrl":"10.1016/j.synbio.2024.11.001","url":null,"abstract":"<div><div>Guvermectin, a purine nucleoside natural product produced by the genus S<em>treptomyces</em>, has recently been registered as a new biopesticide to boost rice yield. Despite its economic and agricultural significance, the regulatory mechanisms of guvermectin biosynthesis remain essentially unknown, hindering industrial production and widespread agricultural application. Here, we examined the roles of two LacI family regulators, <em>gvmR</em> and <em>gvmR2</em>, located within and adjacent to the guvermectin biosynthesis cluster, respectively, in guvermectin production in <em>Streptomyces caniferus</em> NEAU6. GvmR activated the expression of the guvermectin cluster by binding to the promoters of <em>gvmR</em>, <em>gvmA</em>, and <em>O1</em>, while GvmR2 repressed the guvermectin cluster via competitive binding to promoters containing GvmR-binding sites, specifically, a 14-bp palindromic sequences: 5′-RTCATWCGYATGAY-3′ (R = G/A, W = A/T, Y = T/C). Moreover, GvmR indirectly activates the expression of <em>gvmR2</em> while GvmR2 feedback inhibits <em>gvmR</em> transcription, suggesting a functional interaction between the two regulators for coordinating guvermectin production. Overexpression of <em>gvmR</em> via the T7 RNA polymerase-T7 promoter system in the <em>gvmR2</em> mutant significantly elevated guvermectin production by 125 % (from 631 mg L<sup>−1</sup> to 1422 mg L<sup>−1</sup>), compared to the parental strain NEAU6. This suggested that combinatorial manipulation of <em>gvmR</em> and <em>gvmR2</em> is useful for improving guvermectin production. These findings enrich our knowledge of the regulatory network for guvermectin biosynthesis, and offer key targets and effective strategies for high-titer guvermectin production.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 237-246"},"PeriodicalIF":4.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

De novo synthesis of 1-phenethylisoquinoline in engineered Escherichia coli 在工程大肠杆菌中从头合成 1-苯乙基异喹啉

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-09 DOI: 10.1016/j.synbio.2024.10.007

Yaping Mao , Jiangming Zhu , Qian Zhang , Guangyi Wang , Hongkai Fan , Xiaowei Zhang , Yuwei Sun , Yong Wang

{"title":"De novo synthesis of 1-phenethylisoquinoline in engineered Escherichia coli","authors":"Yaping Mao , Jiangming Zhu , Qian Zhang , Guangyi Wang , Hongkai Fan , Xiaowei Zhang , Yuwei Sun , Yong Wang","doi":"10.1016/j.synbio.2024.10.007","DOIUrl":"10.1016/j.synbio.2024.10.007","url":null,"abstract":"<div><div>Phenylethylisoquinoline alkaloids (PIAs) are medicinally important natural products derived from the 1-phenylethylisoquinoline precursor. Heterologous production of the PIAs remains challenging due to the incomplete elucidation of biosynthetic pathway and the lack of proper microbial cell factory designed for precursor enhancement. In this work, an artificial pathway composed of eight enzymes from different species was established for de novo 1-phenylethylisoquinoline biosynthesis in engineered <em>Escherichia coli</em>. The yield of the intermediate 4-hydroxydihydrocinnamaldehyde was optimized through screening various NADP<sup>+</sup>-dependent 2-alkenal reductases, cofactor regeneration and the site-directed mutagenesis of key residues in ChAER1. Subsequently, incorporation of the modified dopamine pathway into an endogenous reductase-deficient <em>E. coli</em> with high tyrosine yield boosted the production of 1-phenylethylisoquinoline, reaching 402.58 mg/L in a 5L fermenter. Our work lays a foundation for the future large-scale production of high value-added 1-phenylethylisoquinoline-related alkaloids.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 271-280"},"PeriodicalIF":4.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing the microbial interactions from Apocynum venetum phyllosphere for natural product discovery 利用芹菜叶球中的微生物相互作用发现天然产品

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-11-08 DOI: 10.1016/j.synbio.2024.11.002

Wei Huang , Xingzhi Jiao , Lingqi Hua , Qianjin Kang , Lili Zhang , Xiaoxia Luo , Linquan Bai

{"title":"Harnessing the microbial interactions from Apocynum venetum phyllosphere for natural product discovery","authors":"Wei Huang , Xingzhi Jiao , Lingqi Hua , Qianjin Kang , Lili Zhang , Xiaoxia Luo , Linquan Bai","doi":"10.1016/j.synbio.2024.11.002","DOIUrl":"10.1016/j.synbio.2024.11.002","url":null,"abstract":"<div><div>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 coexisting neighbors to create a pipeline for BGCs arousing. Coupled with the acquisition of 2760 microbial individuals from the <em>Apocynum venetum</em> (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 <em>Streptomyces</em> sp. LBM_605 and the <em>Rhodococcus</em> sp. LBM_791. This study highlights the intrinsic interactions among coexisting microorganisms within a phyllosphere microbiota as novel avenues for exploring and harnessing NPs.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 262-270"},"PeriodicalIF":4.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0