ダウンロード数 : ?
言語
英語
著者
Ozaki, Taro
Asamizu, Shumpei
Ikeda, Haruo
Omura, Satoshi
Oku, Naoya
Igarashi, Yasuhiro
Tomoda, Hiroshi
Onaka, Hiroyasu
内容記述(抄録等)
Although gt100 thiopeptides have been discovered, the number of validated gene clusters involved in their biosynthesis is lagging. We use genome mining to identify a silent thiopeptide biosynthetic gene cluster responsible for biosynthesis of lactazoles. Lactazoles are structurally unique thiopeptides with a 32-membered macrocycle and a 2-oxazolyl-6-thiazolyl pyridine core. We demonstrate that lactazoles originate from the simplest cluster, containing only six unidirectional genes (lazA to lazF). We show that lazC is involved in the macrocyclization process, leading to central pyridine moiety formation. Substitution of the endogenous promoter with a strong promoter results in an approximately 30-fold increase in lactazole A production and mutagenesis of lazC precursor gene in production of two analogs. Lactazoles do not exhibit antimicrobial activity but may modulate signaling cascades triggered by bone morphogenetic protein. Our approach facilitates the production of a more diverse set of thiopeptide structures, increasing the semisynthetic repertoire for use in drug development.
掲載誌名
Chemistry & biology
21
5
開始ページ
679
終了ページ
688
ISSN
10745521
発行日
2014-05-22
DOI
PubMed ID
NCID
AA11072585
出版者
Elsevier
資料タイプ
学術雑誌論文
権利関係
Copyright © 2014 Elsevier Ltd. All rights reserved.
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部局
生物資源科学部