Cao Zhiqin, Li Shaoyang, Lv Jianming, Gao Hao, Chen Guodong, Awakawa Takayoshi, Abe Ikuro, Yao Xinsheng, Hu Dan
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, China.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Acta Pharm Sin B. 2019 Mar;9(2):433-442. doi: 10.1016/j.apsb.2018.10.007. Epub 2018 Oct 30.
Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.
夫西地酸是唯一一种已在临床上使用的夫西烷型抗生素。然而，真菌中这种重要分子的生物合成过程却鲜为人知。我们最近阐明了夫西烷型抗生素黄青霉素的生物合成，这为我们识别夫西地酸可能的基因簇（簇）提供了线索。该基因簇由八个基因组成，其中六个在黄青霉素基因簇中是保守的，除了 和 。将这两个基因导入表达保守的六个基因的 NSAR1 中导致了夫西地酸的产生。对 和 的逐步导入表明这两个基因独立发挥作用，没有严格的反应顺序。值得注意的是，我们在 簇中鉴定出两个短链脱氢酶/还原酶基因 和 ，它们在 3-酮还原中表现出相反的立体选择性。这是关于夫西地酸生物合成和异源表达的首次报道。
