Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074

Heterologous expression has emerged as an effective strategy in activating <i>Streptomyces</i> cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster <i>spi</i> derived from marine <i&...

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Main Authors: Xiaoting Zhang, Falei Zhang, Chen Li, Jiayi Li, Xiao Xu, Tianjiao Zhu, Qian Che, Deihai Li, Guojian Zhang
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/22/11/480
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author Xiaoting Zhang
Falei Zhang
Chen Li
Jiayi Li
Xiao Xu
Tianjiao Zhu
Qian Che
Deihai Li
Guojian Zhang
author_facet Xiaoting Zhang
Falei Zhang
Chen Li
Jiayi Li
Xiao Xu
Tianjiao Zhu
Qian Che
Deihai Li
Guojian Zhang
author_sort Xiaoting Zhang
collection DOAJ
description Heterologous expression has emerged as an effective strategy in activating <i>Streptomyces</i> cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster <i>spi</i> derived from marine <i>Streptomyces</i> sp. HDN155000 in the chassis host <i>Streptomyces albus</i> J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (<b>2</b>) contains a rare thiomethyl group, angumycinone T (<b>4</b>) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (<b>3</b>) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.
format Article
id doaj-art-efe072b239c84003aec1e88dd6fdf8d6
institution OA Journals
issn 1660-3397
language English
publishDate 2024-10-01
publisher MDPI AG
record_format Article
series Marine Drugs
spelling doaj-art-efe072b239c84003aec1e88dd6fdf8d62025-08-20T02:04:58ZengMDPI AGMarine Drugs1660-33972024-10-01221148010.3390/md22110480Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074Xiaoting Zhang0Falei Zhang1Chen Li2Jiayi Li3Xiao Xu4Tianjiao Zhu5Qian Che6Deihai Li7Guojian Zhang8Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaHeterologous expression has emerged as an effective strategy in activating <i>Streptomyces</i> cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster <i>spi</i> derived from marine <i>Streptomyces</i> sp. HDN155000 in the chassis host <i>Streptomyces albus</i> J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (<b>2</b>) contains a rare thiomethyl group, angumycinone T (<b>4</b>) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (<b>3</b>) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.https://www.mdpi.com/1660-3397/22/11/480heterologous expressionII PKSmarine <i>Streptomyces</i>angucycline
spellingShingle Xiaoting Zhang
Falei Zhang
Chen Li
Jiayi Li
Xiao Xu
Tianjiao Zhu
Qian Che
Deihai Li
Guojian Zhang
Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074
Marine Drugs
heterologous expression
II PKS
marine <i>Streptomyces</i>
angucycline
title Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074
title_full Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074
title_fullStr Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074
title_full_unstemmed Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074
title_short Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in <i>Streptomyces albus</i> J1074
title_sort heterologous expression of type ii pks gene cluster leads to diversified angucyclines in i streptomyces albus i j1074
topic heterologous expression
II PKS
marine <i>Streptomyces</i>
angucycline
url https://www.mdpi.com/1660-3397/22/11/480
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