基于基因组挖掘的一个新的吡嗪酮类天然产物的发现
收稿日期: 2016-02-18
修回日期: 2016-03-01
网络出版日期: 2016-03-18
基金资助
国家自然科学基金（Nos.81373307&81473124）资助项目.
Discovery of a New Pyrazinone Natural Product by Genome Mining
Received date: 2016-02-18
Revised date: 2016-03-01
Online published: 2016-03-18
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 81373307 & 81473124).
采用次级代谢产物基因组挖掘的方法，扫描链霉菌Streptomyces sp. TP-A0365的基因组序列，找到一个新的负责吡嗪酮类天然产物生物合成的非核糖体肽合成酶（NRPS）编码基因. 通过敲除该NRPS基因中断相关化合物的生物合成途径，对比突变菌株和原始菌株（来源于链霉菌Streptomyces sp. TP-A0365的工程菌株TG1301）的发酵产物，我们在原始菌株的发酵粗提液中捕捉到了突变株不再产生的化合物1. 从原始菌株20 L发酵液中分离并鉴定了化合物1的化学结构，其结构为3-异丙基-7，8-二氢吡咯并[1，2-a]吡嗪-4（6H）-酮，是一个新的吡嗪酮类化合物，命名为provalin.
亢文佳 , 吴晟 , 华会明 , 潘海学 , 唐功利 . 基于基因组挖掘的一个新的吡嗪酮类天然产物的发现[J]. 有机化学, 2016 , 36(7) : 1696 -1699 . DOI: 10.6023/cjoc201602016
The genomic sequences of Streptomyces sp. TP-A0365 were scanned using a secondary metabolite genome mining approach. A new nonribosomal peptide synthetase (NRPS) gene responsible for the biosynthesis of an unknown pyrazinone compound was found. The biosynthetic pathway of related compound was disrupted by inactivating the NRPS gene. Comparing the fermentation products of the mutant strain and the original strain (TG1301 derived from Streptomyces sp. TP-A0365), we caught compound 1 which disappeared in the mutant strain. Compound 1 was isolated from 20 L fermentation cultures of the original strain and its structure was established as 3-isopropyl-7,8-dihydropyrrolo[1,2-a]pyrazin-4(6H)-one, a new pyrazinone compound designated as provalin
Key words： pyrazinone; Streptomyces; genome mining; biosynthesis
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