Incorporation of nonmethyl branches by lsoprenoid-like logic:: Multiple β-alkylation events in the biosynthesis of myxovirescin A1
Incorporation of nonmethyl branches by lsoprenoid-like logic:: Multiple β-alkylation events in the biosynthesis of myxovirescin A1
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DOI：
10.1016/j.chembiol.2007.06.008
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发表时间：
2007-07-01
影响因子：
--
通讯作者：
Walsh, Christopher T.
中科院分区：
文献类型：
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作者：
Calderone, Christopher T.;Iwig, David F.;Walsh, Christopher T.
预计几种聚酮次级代谢产物在生物合成期间经历类异戊二烯样β-烷基化。一种这样的次级代谢产物是粘病毒素A1，由黄色粘球菌产生。粘病毒素是特别感兴趣的，因为它似乎经历两种不同的β-烷基化。此外，粘病毒素生物合成基因簇缺乏合成其他β-分支次级代谢物所需的串联巯基化结构域。为了探索粘病毒素中β-分支的起源，我们异源过表达预测负责粘病毒素β-烷基化的蛋白质，并在体外模型底物上重建其活性。我们的研究结果证实，粘病毒素在其生物合成过程中经历了两次类异戊二烯样β-烷基化，包括前所未有的β-乙基化。其生物合成的研究应阐明的范围和要求类异戊二烯生物合成逻辑聚酮化合物的背景下。
Several polyketide secondary metabolites are predicted to undergo isoprenoid-like beta-alkylations during biosynthesis. One such secondary metabolite is myxovirescin A1, produced by Myxococcus xanthus. Myxovirescin is of special interest in that it appears to undergo two distinct beta-alkylations. Additionally, the myxovirescin biosynthetic gene cluster lacks tandem thiolation domains required in the synthesis of other beta-branched secondary metabolites. To probe the origins of the beta-branches in myxovirescin, we heterologously overexpressed the proteins predicted to be responsible for myxovirescin beta-alkylation and reconstituted their activities in vitro on model substrates. Our results confirm that myxovirescin undergoes two isoprenoid-like beta-alkylations during its biosynthesis, including an unprecedented beta-ethylation. The study of its biosynthesis should shed light on the scope and requirements for isoprenoid-like biosynthetic logic in a polyketide context.