Cloning and heterologous expression of sansanmycin biosynthetic gene cluster in Streptomyces coelicolor
10.16438/j.0513-4870.2018-0295
- VernacularTitle:Sansanmycin生物合成基因簇在天蓝色链霉菌中的异源表达
- Author:
Jia-hui FAN
1
;
Yuan-yuan SHI
1
;
Zhi-bo JIANG
1
;
Xing-xing LI
1
;
Xuan LEI
1
;
Yun-ying XIE
1
;
Li-fei WANG
1
;
Bin HONG
1
Author Information
1. Key Laboratory of Biotechnology of Antibiotics of National Health Commission of PRC, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
- Publication Type:SPECIAL REPORTS
- Keywords:
heterologous expression;
Streptomyces coelicolor;
sansanmycin analogue
- From:
Acta Pharmaceutica Sinica
2018;53(6):895-902
- CountryChina
- Language:Chinese
-
Abstract:
Sansanmycins (SSs), produced by Streptomyces sp. SS, belong to uridyl peptide antibiotics which exhibit a good inhibitory effect on Mycobacterium tuberculosis and Pseudomonas aeruginosa. They share a unique chemical scaffold with a 4',5'-enamide-3'-deoxyuridine attached to DABA (N-methyl-2,3-diaminobutyryl) which was located in the peptide chain through peptide bond. In order to study the function of related genes and to employ synthetic biology to gain new SS derivatives, we obtained a complete SS biosynthetic gene cluster and heterologously expressed it in Streptomyces coelicolor M1146, M1152 and M1154. Fermentation broth of the recombinant strains were detected using HPLC and HPLC-MS/MS, and the result showed that SS-A was successfully produced in the three strains, and its production level in S. coelicolor M1154 was similar to the original wild type strain. In addition, a potential SS analogue named as SS-1154 was discovered from the fermentation broth of S. coelicolor M1154.