Identification of Elaiophylin Skeletal Variants from the Indonesian Streptomyces sp. ICBB 9297.
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.
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Corvallis, Oregon 97331-3507, United States.
Yan
Y
Sheng
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Corvallis, Oregon 97331-3507, United States.
Phillip W
PW
Lam
Indonesian Center for Biodiversity and Biotechnology , ICBB-Complex, JI. Cilubang Nagrak No. 62, Situgede, Bogor 16115, Indonesia.
Salmah
S
Shahab
Indonesian Center for Biodiversity and Biotechnology , ICBB-Complex, JI. Cilubang Nagrak No. 62, Situgede, Bogor 16115, Indonesia.|Department of Soil Science and Land Resources, Faculty of Agriculture, Bogor Agricultural University , Bogor, Indonesia.
Dwi Andreas
DA
Santosa
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Corvallis, Oregon 97331-3507, United States.
Philip J
PJ
Proteau
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Corvallis, Oregon 97331-3507, United States.
T Mark
TM
Zabriskie
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University , Corvallis, Oregon 97331-3507, United States.
Taifo
T
Mahmud
D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry; D020134:Catalytic Domain; D007214:Indonesia; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects; D048630:Polyketide Synthases / Q000378:metabolism; D012988:Soil Microbiology; D013302:Streptomyces / Q000737:chemistry*
D000214:Acyl Coenzyme A; D000900:Anti-Bacterial Agents; D018942:Macrolides; C015357:methylmalonyl-coenzyme A; C033279:elaiophylin; D048630:Polyketide Synthases; D000217:Acyltransferases