New Rimocidin/CE-108 Derivatives Obtained by a Crotonyl-CoA Carboxylase/Reductase Gene Disruption in Streptomyces diastaticus var. 108: Substrates for the Polyene Carboxamide Synthase PcsA.
New Rimocidin/CE-108 Derivatives Obtained by a Crotonyl-CoA Carboxylase/Reductase Gene Disruption in Streptomyces diastaticus var. 108: Substrates for the Polyene Carboxamide Synthase PcsA.
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DOI：
10.1371/journal.pone.0135891
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Seco EM
中科院分区：
文献类型：
--
作者：
Escudero L;Al-Refai M;Nieto C;Laatsch H;Malpartida F;Seco EM
编码巴豆酰辅酶A羧化酶/还原酶的rimJ基因位于由淀粉链霉菌变种产生的属于多烯大环内酯类的两种聚酮化合物（CE-108和rimocidin）的生物合成基因簇内。108.通过插入失活破坏rimJ产生了重组菌株，该重组菌株过量产生除亲本CE-108（2a）和rimocidin（4a）之外的新的多烯衍生物。其中之一CE-108 D（3a）的结构解析证实了引入了用于延伸步骤13的替代延伸剂单元。其他化合物也过量产生的rimJ破坏剂的发酵液。新化合物是先前描述的多烯羧酰胺合酶PcsA的体内底物。组成型表达pcsA基因的rimJ破坏菌株允许过量生产CE-108 E（3b），CE-108 D（3a）的相应羧酰胺衍生物，具有改善的药理学性质。
The rimJ gene, which codes for a crotonyl-CoA carboxylase/reductase, lies within the biosynthetic gene cluster for two polyketides belonging to the polyene macrolide group (CE-108 and rimocidin) produced by Streptomyces diastaticus var. 108. Disruption of rimJ by insertional inactivation gave rise to a recombinant strain overproducing new polyene derivatives besides the parental CE-108 (2a) and rimocidin (4a). The structure elucidation of one of them, CE-108D (3a), confirmed the incorporation of an alternative extender unit for elongation step 13. Other compounds were also overproduced in the fermentation broth of rimJ disruptant. The new compounds are in vivo substrates for the previously described polyene carboxamide synthase PcsA. The rimJ disruptant strain, constitutively expressing the pcsA gene, allowed the overproduction of CE-108E (3b), the corresponding carboxamide derivative of CE-108D (3a), with improved pharmacological properties.