Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
Org Biomol Chem. 2011 Feb 21;9(4):1201-11. doi: 10.1039/c0ob00654h. Epub 2010 Dec 14.
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.
从澳大利亚的两个链霉菌分离物的发酵产物的化学分析中，得到了所有已知的和 12 种新的罕见的雷弗霉素类聚酮螺旋缩酮，包括半琥珀酸、半富马酸和半呋喃酸酯。雷弗霉素的鉴定借助于 HPLC-DAD-MS 和 HPLC-DAD-SPE-NMR 方法学，并通过详细的光谱分析确定了结构。对一个前所未有的半琥珀酸酯：酮缩醛-琥珀酰平衡的结构和机制要求进行了定义，并为提出雷弗霉素 4'-甲酯和 5,6-螺缩酮是人工制品提供了依据。提出了一个合理的雷弗霉素聚酮生物合成的假设，需要一个 2-甲基琥珀酰辅酶 A 起始单元，灵活地掺入 C(6-8)聚酮链延伸和二酸酯化单元。通过共代谢物进行的结构活性关系研究用于评估雷弗霉素的抗癌、抗菌和抗真菌特性。
