Identification of Elaiophylin Skeletal Variants from the Indonesian Streptomyces sp. ICBB 9297

Yan Sheng, Phillip W. Lam, Salmah Shahab, Dwi Andreas Santosa, Philip J. Proteau, Mark Zabriskie, Taifo Mahmud

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2768-2775
Number of pages8
JournalJournal of Natural Products
Volume78
Issue number11
DOIs
StatePublished - Nov 25 2015
Externally publishedYes

Fingerprint

Streptomyces
Polyketide Synthases
Malonyl Coenzyme A
Acyltransferases
Macrocyclic Compounds
Mycobacterium smegmatis
Polyketides
Macrolides
Bioinformatics
elaiophylin
Computational Biology
Skeleton
Staphylococcus aureus
Catalytic Domain
Bacteria
Soil
Soils
Amino Acids
Substrates

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine

Cite this

Identification of Elaiophylin Skeletal Variants from the Indonesian Streptomyces sp. ICBB 9297. / Sheng, Yan; Lam, Phillip W.; Shahab, Salmah; Santosa, Dwi Andreas; Proteau, Philip J.; Zabriskie, Mark; Mahmud, Taifo.

In: Journal of Natural Products, Vol. 78, No. 11, 25.11.2015, p. 2768-2775.

Research output: Contribution to journalArticle

Sheng, Yan ; Lam, Phillip W. ; Shahab, Salmah ; Santosa, Dwi Andreas ; Proteau, Philip J. ; Zabriskie, Mark ; Mahmud, Taifo. / Identification of Elaiophylin Skeletal Variants from the Indonesian Streptomyces sp. ICBB 9297. In: Journal of Natural Products. 2015 ; Vol. 78, No. 11. pp. 2768-2775.
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