Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy.
Acta Pharm Sin B
; 11(6): 1676-1685, 2021 Jun.
Article
en En
| MEDLINE
| ID: mdl-34221876
ABSTRACT
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 structureâactivity 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Acta Pharm Sin B
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS