Biosynthesis of an anti- tuberculosis sesterterpenoid asperterpenoid A

被引:32
作者
Huang, Jia-Hua [1 ]
Lv, Jian-Ming [1 ]
Wang, Qiao-Zhen [1 ]
Zou, Jian [1 ]
Lu, Yong-Jun [2 ]
Wang, Qing-Lin [2 ]
Chen, Dong-Ni [3 ]
Yao, Xin-Sheng [1 ]
Gao, Hao [1 ]
Hu, Dan [1 ]
机构
[1] Jinan Univ, Guangdong Prov Key Lab Pharmacodynam Constiuents, Coll Pharm, Inst Tradit Chinese Med & Nat Prod, Guangzhou 510632, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Sch Marine Sci, Guangzhou 510275, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
GENOME MINING APPROACH; TERPENE SYNTHASES; DISCOVERY;
D O I
10.1039/c8ob02832j
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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 M.
引用
收藏
页码:248 / 251
页数:4
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