| Autor: |
Xiaojun Song, Jianming Lv, Zhiqin Cao, Huiyun Huang, Guodong Chen, Takayoshi Awakawa, Dan Hu, Hao Gao, Ikuro Abe, Xinsheng Yao |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Acta Pharmaceutica Sinica B, Vol 11, Iss 6, Pp 1676-1685 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2211-3835 |
| DOI: |
10.1016/j.apsb.2020.12.007 |
| Popis: |
Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P1, are fungi-derived antimicrobials with little cross-resistance to commonly used antibiotics. Generation of new fusidane-type derivatives is therefore of great value, but this is hindered by available approaches. Here, we developed a stochastic combinational strategy by random assembly of all the post-tailoring genes derived from helvolic acid, fusidic acid, and cephalosporin P1 biosynthetic pathways in a strain that produces their common intermediate. Among a total of 27 gene combinations, 24 combinations produce expected products and afford 58 fusidane-type analogues, of which 54 are new compounds. Moreover, random gene combination can induce unexpected activity of some post-tailoring enzymes, leading to a further increase in chemical diversity. These newly generated derivatives provide new insights into the structure‒activity relationship of fusidane-type antibiotics. The stochastic combinational strategy established in this study proves to be a powerful approach for expanding structural diversity of natural products. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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