Heterologous Expression of Epoxomicin in Escherichia coli.

IF 3.7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
ACS Synthetic Biology Pub Date : 2024-09-20 Epub Date: 2024-08-08 DOI:10.1021/acssynbio.4c00430
Sarah R Messenger, David F Ackerley, Mark J Calcott
{"title":"Heterologous Expression of Epoxomicin in <i>Escherichia coli</i>.","authors":"Sarah R Messenger, David F Ackerley, Mark J Calcott","doi":"10.1021/acssynbio.4c00430","DOIUrl":null,"url":null,"abstract":"<p><p>Epoxomicin is an epoxyketone proteasome inhibitor with synthetic derivatives approved or under investigation for treatment of multiple myeloma. To leverage the advantages of <i>Escherichia coli</i> as a rapidly growing and readily engineered host for the production of epoxomicin and analogues, we expressed codon-optimized versions of the epoxomicin biosynthetic genes, <i>epxD, epxE</i>, and <i>epxF</i>. Epoxomicin was detected, but the major product was a ketone resulting from α,β-keto acid precursor decarboxylation. Epoxomicin yield was improved by altering the copy numbers of each gene and creating a fusion of <i>epxE</i> and <i>epxF</i>. Our optimized system offers promise for efficient engineering and biosynthesis of improved epoxomicin analogues.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Synthetic Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acssynbio.4c00430","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0

Abstract

Epoxomicin is an epoxyketone proteasome inhibitor with synthetic derivatives approved or under investigation for treatment of multiple myeloma. To leverage the advantages of Escherichia coli as a rapidly growing and readily engineered host for the production of epoxomicin and analogues, we expressed codon-optimized versions of the epoxomicin biosynthetic genes, epxD, epxE, and epxF. Epoxomicin was detected, but the major product was a ketone resulting from α,β-keto acid precursor decarboxylation. Epoxomicin yield was improved by altering the copy numbers of each gene and creating a fusion of epxE and epxF. Our optimized system offers promise for efficient engineering and biosynthesis of improved epoxomicin analogues.

Abstract Image

在大肠杆菌中异源表达环氧霉素。
环氧霉素是一种环氧酮蛋白酶体抑制剂,其合成衍生物已被批准或正在研究用于治疗多发性骨髓瘤。为了利用大肠杆菌作为快速生长和易于改造的宿主的优势来生产环氧霉素及其类似物,我们表达了经过密码子优化的环氧霉素生物合成基因 epxD、epxE 和 epxF。我们检测到了环氧霉素,但主要产物是由α,β-酮酸前体脱羧产生的酮。通过改变每个基因的拷贝数和创建 epxE 与 epxF 的融合体,提高了环氧霉素的产量。我们的优化系统为高效工程和生物合成改良的环氧霉素类似物提供了希望。
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
CiteScore
8.00
自引率
10.60%
发文量
380
审稿时长
6-12 weeks
期刊介绍: The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.
×
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:481959085
Book学术官方微信