黑曲霉着陆垫系统的开发及其在过量生产莫纳可林中的应用 J.

IF 6.1 1区 生物学 Q1 MICROBIOLOGY
Linlin Yao, Junwei Zheng, Bin Wang, Li Pan
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引用次数: 0

摘要

黑曲霉是一种强大而高效的细胞工厂,具有作为底盘细胞合成有价值产品的潜力。利用微生物细胞工厂生产他汀类药物合成的前体物质 Monacolin J,可替代化学合成,满足日益增长的市场需求。然而,精确的大片段基因编辑需求和合适整合位点的可用性阻碍了该菌株的应用。在此,我们结合 ATAC-seq、H3K4me3 表观遗传学数据集,确定了黑僵菌的中性整合位点。接下来,我们开发了一种着陆垫系统,用于一步整合黑僵菌中的 MJ 生物合成基因簇(BGC)。此外,我们还优化了前体模块供应、NADPH 辅助因子供应模块、消除氧化应激压力模块和转运模块,以提高 MJ 的产量。最后,我们采用多拷贝整合策略对 MJ BGC 进行了快速整合,在 500 mL 摇床水平上使 MJ 滴度达到 1851.52 mg/L。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development of a landing pad system for Aspergillus niger and its application in the overproduction of monacolin J.

Aspergillus niger is a powerful and efficient cell factory, with the potential to synthesize valuable products as chassis cells. The use of microbial cell factories to produce monacolin J, a precursor for statin synthesis, as an alternative to chemical synthesis could meet increasing market demand. However, the need for precise large fragment gene editing and the availability of suitable integration loci hinders the application of this strain. Herein, we identified neutral integration sites of A. niger based on the combination of ATAC-seq, H3K4me3 epigenetic datasets. Next, a landing pad system was developed for the one-step integration of the MJ biosynthesis gene cluster (BGC) in A. niger. Furthermore, we optimized the precursor module supply, the auxiliary factor supply module of NADPH, the module for eliminating oxidative stress pressure, and the transporter module to improve the production of MJ. Finally, a multi-copy integration strategy was applied to the rapid integration of MJ BGC, achieving MJ titer up to 1851.52 mg/L at the 500 mL shaker level.

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来源期刊
Microbiological research
Microbiological research 生物-微生物学
CiteScore
10.90
自引率
6.00%
发文量
249
审稿时长
29 days
期刊介绍: Microbiological Research is devoted to publishing reports on prokaryotic and eukaryotic microorganisms such as yeasts, fungi, bacteria, archaea, and protozoa. Research on interactions between pathogenic microorganisms and their environment or hosts are also covered.
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