Incomplete beta-ketone processing as a mechanism for polyene structural variation in the FR-008/candicidin complex.
Chem Biol
; 15(6): 629-38, 2008 Jun.
Article
in En
| MEDLINE
| ID: mdl-18559273
ABSTRACT
FR-008/candicidin is a heptaene macrolide with established antifungal activity, produced by Streptomyces sp. FR-008 as a complex mixture of compounds. Here, six components (FR-008-I to -VI) of the FR-008/candicidin complex were determined; III, V, and VI were confirmed as natural products, principally differing from each other at C-3 and C-9, while the other three were believed to originate from the respective conversions of the natural ones in vitro. Inactivation of KR21 and DH18, respectively, abolished production of V carrying a C-3 hydroxyl, and VI carrying a C-9 methylene. Combined inactivation created a mutant producing only III, with a C-3 ketone and a C-9 hydroxyl, and having antifungal activity superior to V and comparable to VI. Incomplete activities of KR21 and DH18 were, therefore, unambiguously identified as being involved in structural variations of FR-008 complex.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Candicidin
/
Ketones
Language:
En
Journal:
Chem Biol
Journal subject:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Year:
2008
Document type:
Article
Affiliation country:
China