Journal
CHEMISTRY & BIOLOGY
Volume 11, Issue 1, Pages 33-45Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2003.12.014
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K02AI051689] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI51689] Funding Source: Medline
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A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140. The boundaries of the Inm cluster were defined by systematic inactivation of open reading frames within the sequenced region. The Inm cluster spans 61.3 kb of DNA and consists of 27 genes encoding nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), hybrid NRPS-PKS, resistance, regulatory, and tailoring enzymes, as well as proteins of unknown function. A model for LNM biosynthesis is proposed, central to which is the LNM hybrid NRPS-PKS megasynthetase consisting of discrete (LnmQ and LnmP) and modular (Lnml) NRPS, acyltransferase-less PKS (LnmG, Lnml, and LnmJ), and PKS modules with unusual domain organization. These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis.
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