A Plug-and-Play T7 Expression System for Heterologous Production of Lanthipeptides in Bacillus subtilis

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub Date : 2024-10-31 DOI:10.1021/acssynbio.4c0059410.1021/acssynbio.4c00594

Chengyou Shi, and , Huimin Zhao*,

引用次数: 0

Abstract

Ribosomally synthesized lanthionine-containing peptides (lanthipeptides) have emerged as a promising source of antimicrobials against multidrug resistance pathogens. An effective way to discover and engineer lanthipeptides is through heterologous expression of their biosynthetic gene clusters (BGCs) in a host of choice. Here we report a plug-and-play pathway refactoring strategy for rapid evaluation of lanthipeptide BGCs in Bacillus subtilis based on the T7 expression system. As a proof of concept, we used this strategy to not only observe the successful production of a known lanthipeptide haloduracin β but also discover two new human-microbiota-derived lanthipeptides that previously failed to be produced in Escherichia coli. The resulting B. subtilis plug-and-play T7 expression system should enable the genome mining of new lanthipeptides in a high-throughput manner.

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在枯草芽孢杆菌中异源生产肽的即插即用 T7 表达系统

核糖体合成的含兰硫宁肽（兰硫肽）已成为一种很有前景的抗菌剂，可用于对抗具有多重耐药性的病原体。发现和设计含兰硫宁肽的有效方法是在宿主中异源表达其生物合成基因簇（BGC）。在此，我们报告了一种即插即用的路径重构策略，该策略基于 T7 表达系统，可在枯草芽孢杆菌中快速评估anthipeptide BGCs。作为概念验证，我们利用这一策略不仅观察到了已知anthipeptide haloduracin β的成功生产，还发现了两种新的源自人类微生物区系的anthipeptide，这两种anthipeptide以前在大肠杆菌中无法生产。由此产生的枯草杆菌即插即用 T7 表达系统将能以高通量的方式进行新兰肽的基因组挖掘。

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来源期刊

ACS Synthetic Biology 生物-

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.