The Phormidolide Biosynthetic Gene Cluster: A trans-AT PKS Pathway Encoding a Toxic Macrocyclic Polyketide
The Phormidolide Biosynthetic Gene Cluster: A trans-AT PKS Pathway Encoding a Toxic Macrocyclic Polyketide
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DOI：
10.1002/cbic.201500467
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发表时间：
2016-01-15
期刊：
影响因子：
3.2
通讯作者：
Gerwick, William H.
中科院分区：
文献类型：
--
作者：
Bertin, Matthew J.;Vulpanovici, Alexandra;Gerwick, William H.
Phormidtenol是由培养的丝状海洋蓝细菌产生的聚酮化合物，并包含16元大环内酯。其复杂的结构是公认的来自聚酮合成酶途径，但具有独特的和有趣的结构特征，促使人们有兴趣研究其生物合成的起源。稳定同位素掺入实验证实了该化合物的聚酮化合物性质。我们通过基因组测序和生物信息学分析进一步鉴定了phormiddle基因簇（phm）。两个独立的反式酰基转移酶（trans-AT）ORF沿着在聚酮合成酶（PKS）大合成酶内具有KS-AT适配器区（ATd），表明phormiddle基因簇是一个trans-AT PKS。从乙酸盐掺入和随后酮基还原的模式分析中获得的见解促使我们重新评估位于沿着线性聚酮链的phormiddle羟基的立体化学。
Phormidolide is a polyketide produced by a cultured filamentous marine cyanobacterium and incorporates a 16-membered macrolactone. Its complex structure is recognizably derived from a polyketide synthase pathway, but possesses unique and intriguing structural features that prompted interest in investigating its biosynthetic origin. Stable isotope incorporation experiments confirmed the polyketide nature of this compound. We further characterized the phormidolide gene cluster (phm) through genome sequencing followed by bioinformatic analysis. Two discrete trans-type acyltransferase (trans-AT) ORFs along with KS-AT adaptor regions (ATd) within the polyketide synthase (PKS) megasynthases, suggest that the phormidolide gene cluster is a trans-AT PKS. Insights gained from analysis of the mode of acetate incorporation and ensuing keto reduction prompted our reevaluation of the stereochemistry of phormidolide hydroxy groups located along the linear polyketide chain.