Reveromycins Revealed: New polyketide spiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural products vs. artifacts
Reveromycins Revealed: New polyketide spiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural products vs. artifacts
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DOI：
10.1039/c0ob00654h
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Capon, Robert J.
中科院分区：
文献类型：
--
作者：
Fremlin, Leith;Farrugia, Michelle;Capon, Robert J.
从两个澳大利亚链霉菌菌株的发酵产物的化学分析产生了所有四个已知的和12个新的例子罕见的逆转录霉素类的聚酮螺缩酮，包括半琥珀酸，半琥珀酸和半呋喃酸。利用HPLC-DAD-MS和HPLC-DAD-SPE-NMR方法对Reveromycins进行了鉴定，并通过详细的光谱分析对其结构进行了归属。定义了前所未有的半琥珀酸酯：缩酮-琥珀酰平衡的结构和机理要求，并为提出回复霉素4 '-甲酯和5，6-螺缩酮是人工产物提供了基础。提出了一种合理的回复霉素聚酮生物合成，需要2-甲基琥珀酰辅酶A起始单元，并灵活地掺入C（6-8）聚酮链延伸和二酸酯化单元。通过共代谢物的构效关系研究来评估逆转霉素的抗癌、抗菌和抗真菌特性。
Chemical analysis of fermentation products from two Australian Streptomyces isolates yielded all four known and twelve new examples of the rare reveromycin class of polyketide spiroketals, including hemi-succinates, hemi-fumarates and hemi-furanoates. Reveromycins were identified with the aid of HPLC-DAD-MS and HPLC-DAD-SPE-NMR methodology, and structures were assigned by detailed spectroscopic analysis. The structural and mechanistic requirements for an unprecedented hemi-succinate : ketal-succinyl equilibrium were defined and provided a basis for proposing that reveromycin 4'-methyl esters and 5,6-spiroketals were artifacts. A plausible reveromycin polyketide biosynthesis is proposed, requiring a 2-methylsuccinyl-CoA starter unit, with flexible incorporation of a C(6-8) polyketide chain extension and diacid esterification units. Structure activity relationship investigations by co-metabolites were used to assess the anticancer, antibacterial and antifungal properties of reveromycins.