{"title":"用甘油生产芳香酯的细菌平台","authors":"Liangyu Lu, Xiaolei Wang, Tong Wang, Xiaolin Shen, Xinxiao Sun, Pingfang Tian, Yajun Yan, Jens Nielsen, Jia Wang, Qipeng Yuan","doi":"10.1038/s44286-024-00148-9","DOIUrl":null,"url":null,"abstract":"Aromatic esters possess flavor and fragrance qualities that are widely used in the food, pharmaceutical and cosmetic industries. However, microbial production of these compounds is hampered by a limited understanding of the natural biosynthetic pathway and the relatively low titer and yield. This study establishes a microbial platform for the efficient production of various aromatic esters. A systematic engineering strategy was developed, involving reshaping the substrate access tunnel to enhance enzyme substrate specificity, shifting acetyl coenzyme A metabolic pathways to improve cofactor supply and engineering a dynamic regulation system to redistribute the carbon flux from cell growth toward product synthesis. The implementation of these approaches led to the production of 10.4 g l–1 benzyl benzoate, representing a 4,700-fold increase in titer compared with the initial strain. This work showcases a bacterial platform for the efficient production of aromatic esters and offers insights into overcoming challenges in microbial cell factory construction. Biosynthesis of aromatic esters is challenged by unclear natural pathways and low efficiency. This study presents a bacterial platform for efficient production, using systematic engineering strategies including enzyme identification, reshaping enzyme tunnels and automating cellular resource allocation to enhance output.","PeriodicalId":501699,"journal":{"name":"Nature Chemical Engineering","volume":"1 12","pages":"751-764"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A bacterial platform for producing aromatic esters from glycerol\",\"authors\":\"Liangyu Lu, Xiaolei Wang, Tong Wang, Xiaolin Shen, Xinxiao Sun, Pingfang Tian, Yajun Yan, Jens Nielsen, Jia Wang, Qipeng Yuan\",\"doi\":\"10.1038/s44286-024-00148-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Aromatic esters possess flavor and fragrance qualities that are widely used in the food, pharmaceutical and cosmetic industries. However, microbial production of these compounds is hampered by a limited understanding of the natural biosynthetic pathway and the relatively low titer and yield. This study establishes a microbial platform for the efficient production of various aromatic esters. A systematic engineering strategy was developed, involving reshaping the substrate access tunnel to enhance enzyme substrate specificity, shifting acetyl coenzyme A metabolic pathways to improve cofactor supply and engineering a dynamic regulation system to redistribute the carbon flux from cell growth toward product synthesis. The implementation of these approaches led to the production of 10.4 g l–1 benzyl benzoate, representing a 4,700-fold increase in titer compared with the initial strain. This work showcases a bacterial platform for the efficient production of aromatic esters and offers insights into overcoming challenges in microbial cell factory construction. Biosynthesis of aromatic esters is challenged by unclear natural pathways and low efficiency. This study presents a bacterial platform for efficient production, using systematic engineering strategies including enzyme identification, reshaping enzyme tunnels and automating cellular resource allocation to enhance output.\",\"PeriodicalId\":501699,\"journal\":{\"name\":\"Nature Chemical Engineering\",\"volume\":\"1 12\",\"pages\":\"751-764\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-12-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Chemical Engineering\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.nature.com/articles/s44286-024-00148-9\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Chemical Engineering","FirstCategoryId":"1085","ListUrlMain":"https://www.nature.com/articles/s44286-024-00148-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
芳香酯具有风味和香味的特性,广泛应用于食品、制药和化妆品行业。然而,由于对天然生物合成途径的了解有限,以及相对较低的滴度和产率,这些化合物的微生物生产受到阻碍。本研究建立了高效生产各种芳香酯的微生物平台。研究人员开发了一种系统的工程策略,包括重塑底物通道以增强酶底物特异性,改变乙酰辅酶A代谢途径以改善辅因子供应,以及设计一个动态调节系统以重新分配从细胞生长到产物合成的碳通量。这些方法的实施导致生产10.4 g - 1苯甲酸苄酯,与初始菌株相比,滴度增加了4700倍。这项工作展示了一个有效生产芳香酯的细菌平台,并为克服微生物细胞工厂建设中的挑战提供了见解。芳香酯的生物合成受到天然途径不明确和效率低的挑战。本研究提出了一个高效生产的细菌平台,使用系统工程策略,包括酶鉴定,重塑酶通道和自动化细胞资源分配来提高产量。
A bacterial platform for producing aromatic esters from glycerol
Aromatic esters possess flavor and fragrance qualities that are widely used in the food, pharmaceutical and cosmetic industries. However, microbial production of these compounds is hampered by a limited understanding of the natural biosynthetic pathway and the relatively low titer and yield. This study establishes a microbial platform for the efficient production of various aromatic esters. A systematic engineering strategy was developed, involving reshaping the substrate access tunnel to enhance enzyme substrate specificity, shifting acetyl coenzyme A metabolic pathways to improve cofactor supply and engineering a dynamic regulation system to redistribute the carbon flux from cell growth toward product synthesis. The implementation of these approaches led to the production of 10.4 g l–1 benzyl benzoate, representing a 4,700-fold increase in titer compared with the initial strain. This work showcases a bacterial platform for the efficient production of aromatic esters and offers insights into overcoming challenges in microbial cell factory construction. Biosynthesis of aromatic esters is challenged by unclear natural pathways and low efficiency. This study presents a bacterial platform for efficient production, using systematic engineering strategies including enzyme identification, reshaping enzyme tunnels and automating cellular resource allocation to enhance output.