{"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}
引用次数: 0
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.