Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity.
10.1016/j.apsb.2018.10.007
- Author:
Zhiqin CAO
1
;
Shaoyang LI
1
;
Jianming LV
1
;
Hao GAO
1
;
Guodong CHEN
1
;
Takayoshi AWAKAWA
2
;
Ikuro ABE
2
;
Xinsheng YAO
1
;
Dan HU
1
Author Information
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, China.
2. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
- Publication Type:Journal Article
- Keywords:
Biosynthesis;
Fungi;
Fusidane-type antibiotics;
Fusidic acid;
SDR
- From:
Acta Pharmaceutica Sinica B
2019;9(2):433-442
- CountryChina
- Language:English
-
Abstract:
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.
