抗结核倍半萜asperterpenoid A 的生物合成。
Biosynthesis of an anti-tuberculosis sesterterpenoid asperterpenoid A.
机构信息
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, People's Republic of China.
出版信息
Org Biomol Chem. 2019 Jan 2;17(2):248-251. doi: 10.1039/c8ob02832j.
A putative three-gene cluster for asperterpenoid A was identified. Step-wise reconstitution of this gene cluster in Aspergillus oryzae reveals that astC encodes a sesterterpene cyclase to synthesize preasperterpenoid A, which is dually oxidized by a P450 enzyme AstB to give asperterpenoid A along with a minor product asperterpenoid B, and asperterpenoid A is further oxidized by another P450 eznyme AstA to afford a new sesterterpenoid asperterpenoid C. Unexpectedly, asperterpenoids A and B, but not the final product asperterpenoid C, exhibit potent inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B with IC50 values of 3-6 μM.
鉴定出一个假定的 Asperterpenoid A 三基因簇。在 Aspergillus oryzae 中逐步重建这个基因簇，表明 astC 编码一个甾体环化酶来合成前 Asperterpenoid A，它被 P450 酶 AstB 双重氧化，生成 Asperterpenoid A 以及一个次要产物 Asperterpenoid B，Asperterpenoid A 进一步被另一个 P450 酶 AstA 氧化，得到一个新的甾体化合物 Asperterpenoid C。出乎意料的是，Asperterpenoids A 和 B，但不是最终产物 Asperterpenoid C，对结核分枝杆菌蛋白酪氨酸磷酸酶 B 表现出强烈的抑制活性，IC50 值为 3-6 μM。
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