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隐秘基因簇的异源表达及马杜拉放线菌素A的结构修正

Heterologous expression of the cryptic gene cluster and structural revision of maduralactomycin A.

作者信息

Schwitalla Jan W, Le Ngoc-Thao-Hien, Um Soohyun, Schalk Felix, Brönstrup Mark, Baunach Martin, Beemelmanns Christine

机构信息

Chemical Biology of Microbe-Host Interactions, Hans-Knöll Institute (HKI) Beutenbergstraße 11a 07745 Jena Germany.

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) Campus E8 66123 Saarbrücken Germany

出版信息

RSC Adv. 2023 Nov 22;13(48):34136-34144. doi: 10.1039/d3ra05931f. eCollection 2023 Nov 16.

DOI:10.1039/d3ra05931f
PMID:38019997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10663993/
Abstract

After conducting an analysis of the cryptic cluster region and performing transcriptomic studies, an integrative BAC Vector containing the gene sequence was constructed. The heterologous expression of the cluster in J1074 resulted in the production of the angucyclic product, seongomycin, which allowed for the assesment of its antibacterial, antiproliferative, and antiviral activities. Heterologous production was further confirmed by targeted knock-out experiments involving key regulators of the biosynthetic pathways. We were further able to revise the core structure of maduralactomycin A, using a computational approach.

摘要

在对神秘簇区域进行分析并开展转录组学研究之后，构建了一个包含该基因序列的整合BAC载体。该簇在J1074中的异源表达产生了安古环类产物——生霉素，这使得能够评估其抗菌、抗增殖和抗病毒活性。通过涉及生物合成途径关键调控因子的靶向敲除实验进一步证实了异源生产。我们还能够使用计算方法修订马杜拉放线菌素A的核心结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/043f/10663993/4fa49be9e365/d3ra05931f-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/043f/10663993/4fa49be9e365/d3ra05931f-f7.jpg

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The Natural Product Domain Seeker version 2 (NaPDoS2) webtool relates ketosynthase phylogeny to biosynthetic function.
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