Identification of Elaiophylin Skeletal Variants from the Indonesian Streptomyces sp. ICBB 9297.
J Nat Prod
; 78(11): 2768-75, 2015 Nov 25.
Article
in En
| MEDLINE
| ID: mdl-26510047
ABSTRACT
Four new elaiophylin macrolides (1-4), together with five known elaiophylins (5-9), have been isolated from cultures of the Indonesian soil bacterium Streptomyces sp. ICBB 9297. The new compounds have macrocyclic skeletons distinct from those of the known dimeric elaiophylins in that one or both of the polyketide chains contain(s) an additional pendant methyl group. Further investigations revealed that 1 and 2 were derived from 3 and 4, respectively, during isolation processes. Compounds 1-3 showed comparable antibacterial activity to elaiophylin against Staphylococcus aureus. However, interestingly, only compounds 1 and 3, which contain a pendant methyl group at C-2, showed activity against Mycobacterium smegmatis, whereas compound 2, which has two pendant methyl groups at C-2 and C-2', and the known elaiophylin analogues (5-7), which lack pendant methyl groups at C-2 and/or C-2', showed no activity. The production of 3 and 4 in strain ICBB 9297 indicates that one of the acyltransferase (AT) domains in the elaiophylin polyketide synthases (PKSs) can recruit both malonyl-CoA and methylmalonyl-CoA as substrates. Bioinformatic analysis of the AT domains of the elaiophylin PKSs revealed that the ela_AT7 domain contains atypical active site amino acid residues, distinct from those conserved in malonyl-CoA- or methylmalonyl-CoA-specific ATs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Streptomyces
/
Macrolides
Type of study:
Diagnostic_studies
Country/Region as subject:
Asia
Language:
En
Journal:
J Nat Prod
Year:
2015
Document type:
Article
Affiliation country:
United States