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Biosynthesis of Biscognienyne B Involving a Cytochrome P450-Dependent Alkynylation |
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| Authors: | Dr Jian-Ming Lv Yao-Hui Gao Dr Huan Zhao Prof Takayoshi Awakawa Prof Ling Liu Prof Guo-Dong Chen Prof Xin-Sheng Yao Prof Dan Hu Prof Ikuro Abe Prof Hao Gao |
| Institution: | 1. 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 P. R. China
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632 P. R. China These authors contributed equally to this work.;2. 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 P. R. China These authors contributed equally to this work.;3. College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632 P. R. China;4. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan;5. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101 P. R. China;6. 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 P. R. China |
| Abstract: | The alkyne is a biologically significant moiety found in many natural products and a versatile functional group widely used in modern chemistry. Recent studies have revealed the biosynthesis of acetylenic bonds in fatty acids and amino acids. However, the molecular basis for the alkynyl moiety in acetylenic prenyl chains occurring in a number of meroterpenoids remains obscure. Here, we identify the biosynthetic gene cluster and characterize the biosynthetic pathway of an acetylenic meroterpenoid biscognienyne B based on heterologous expression, feeding experiments, and in vitro assay. This work shows that the alkyne moiety is constructed by an unprecedented cytochrome P450 enzyme BisI, which shows promiscuous activity towards C5 and C15 prenyl chains. This finding provides an opportunity for discovery of new compounds, featuring acetylenic prenyl chains, through genome mining, and it also expands the enzyme inventory for de novo biosynthesis of alkynes. |
| Keywords: | alkynes biosynthesis cytochromes enzymes terpenoids |