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Updated: Aug 8, 2026
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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Biosynthetic gene cluster for the polyenoyltetramic acid alpha-lipomycin
C Bihlmaier1, E Welle, C Hofmann
1Albert-Ludwigs-Universität Freiburg, Institut für Pharmazeutische Wissenschaften, Pharmazeutische Biologie und Biotechnologie, Freiburg, Germany.
Antimicrobial Agents and Chemotherapy
|May 26, 2006
Summary
The Streptomyces aureofaciens Tü117 bacterium
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Streptomyces aureofaciens Tü117 is a gram-positive bacterium.
- This bacterium produces the acyclic polyene antibiotic alpha-lipomycin.
Purpose of the Study:
- To clone and characterize the entire biosynthetic gene cluster (lip gene cluster) responsible for alpha-lipomycin production.
- To elucidate the biosynthetic pathway of alpha-lipomycin.
Main Methods:
- DNA sequencing of a 74-kb region to identify open reading frames (ORFs).
- Analysis of gene homology to polyketide synthases and nonribosomal peptide synthetases.
- Generation of biosynthetic mutants using insertional gene inactivation.
Main Results:
- Identified 28 complete ORFs within the 74-kb region, with 22 belonging to the lip gene cluster.
- Discovered a polyketide synthase locus with an eight-module system and an ORF homologous to nonribosomal peptide synthetases, classifying alpha-lipomycin as a hybrid peptide-polyketide.
- Confirmed the cloned genes' involvement in alpha-lipomycin biosynthesis and gained insights into its unusual pathway.
Conclusions:
- The lip gene cluster encodes the complete biosynthesis of alpha-lipomycin.
- Alpha-lipomycin is a hybrid peptide-polyketide natural product.
- The study provides a foundation for understanding and potentially engineering the biosynthesis of this antibiotic.
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