Enhancing 10-HDA production of Escherichia coli by heterologous expression of MexHID transporter proteins.

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Frontiers in Bioengineering and Biotechnology Pub Date : 2025-06-09 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1590291
Ziting Xu, Chaofan Du, Sheng Gao, Xinrui Yan, Pan Deng, Yuehan Liu, Junqing Wang, Ruiming Wang, Nan Li
{"title":"Enhancing 10-HDA production of <i>Escherichia coli</i> by heterologous expression of MexHID transporter proteins.","authors":"Ziting Xu, Chaofan Du, Sheng Gao, Xinrui Yan, Pan Deng, Yuehan Liu, Junqing Wang, Ruiming Wang, Nan Li","doi":"10.3389/fbioe.2025.1590291","DOIUrl":null,"url":null,"abstract":"<p><p>10-Hydroxy-2-decenoic acid (10-HDA) is a medium-chain α,β-unsaturated carboxylic acid that exists in royal jelly with terminal hydroxylation. It has a broad market value because of its antibacterial, anti-inflammatory, anti-tumor, anti-radiation, and other active functions. The one-step whole-cell catalytic synthesis of 10-HDA by constructing engineered strains has improved the reaction rate to a certain extent compared with the previous two-step method. However, the accumulation of 10-HDA to a certain concentration in engineered <i>Escherichia coli</i> strains will damage the structure and function of cells and even lead to death; this unique antibacterial and antimicrobial activity seriously constrains the production of 10-HDA. In this study, we mined a transporter protein from <i>Pseudomonas aeruginosa</i>, which possesses the ability to efficiently efflux 10-HDA, and constructed a transporter protein overexpression strain by using the multicopy chromosome integration technique, which further improved the efficiency of product efflux, weakened the feedback inhibition of 10-HDA to a certain degree, and increased the substrate conversion rate to 88.6%. 10-HDA was synthesized up to 0.94 g/L by the replenishment flow-addition technique, providing a simple and efficient pathway for the yield breakthrough of 10-HDA biosynthesis.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1590291"},"PeriodicalIF":4.3000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183247/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2025.1590291","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

10-Hydroxy-2-decenoic acid (10-HDA) is a medium-chain α,β-unsaturated carboxylic acid that exists in royal jelly with terminal hydroxylation. It has a broad market value because of its antibacterial, anti-inflammatory, anti-tumor, anti-radiation, and other active functions. The one-step whole-cell catalytic synthesis of 10-HDA by constructing engineered strains has improved the reaction rate to a certain extent compared with the previous two-step method. However, the accumulation of 10-HDA to a certain concentration in engineered Escherichia coli strains will damage the structure and function of cells and even lead to death; this unique antibacterial and antimicrobial activity seriously constrains the production of 10-HDA. In this study, we mined a transporter protein from Pseudomonas aeruginosa, which possesses the ability to efficiently efflux 10-HDA, and constructed a transporter protein overexpression strain by using the multicopy chromosome integration technique, which further improved the efficiency of product efflux, weakened the feedback inhibition of 10-HDA to a certain degree, and increased the substrate conversion rate to 88.6%. 10-HDA was synthesized up to 0.94 g/L by the replenishment flow-addition technique, providing a simple and efficient pathway for the yield breakthrough of 10-HDA biosynthesis.

通过外源表达mexpod转运蛋白提高大肠杆菌10-HDA的产量。
10-羟基-2-十烯酸(10-HDA)是一种存在于蜂王浆中端羟基化的中链α,β-不饱和羧酸。它具有抗菌、抗炎、抗肿瘤、抗辐射等活性功能,具有广阔的市场价值。通过构建工程菌株一步法全细胞催化合成10-HDA,与之前的两步法相比,在一定程度上提高了反应速率。但10-HDA在工程大肠杆菌中积累到一定浓度,会破坏细胞的结构和功能,甚至导致死亡;这种独特的抗菌活性严重限制了10-HDA的产生。本研究从铜绿假单胞菌中挖掘出一种具有高效外排10-HDA能力的转运蛋白,并利用多拷贝染色体整合技术构建转运蛋白过表达菌株,进一步提高了产物外排效率,在一定程度上减弱了10-HDA的反馈抑制作用,将底物转化率提高到88.6%。通过补充流动-添加技术,10-HDA的合成效率达到0.94 g/L,为10-HDA生物合成产量突破提供了一条简单有效的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信