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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
Post-polyketide synthase steps in iso-migrastatin biosynthesis, featuring tailoring enzymes with broad substrate
Ming Ma1, Thomas Kwong, Si-Kyu Lim
1Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458, USA.
Journal of the American Chemical Society
|February 12, 2013
Summary
Researchers explored the iso-migrastatin (iso-MGS) biosynthetic gene cluster in Streptomyces platensis. They identified novel products from an acyltransferase (AT)-less type I polyketide synthase (PKS) and detailed the roles of tailoring enzymes.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- The iso-migrastatin (iso-MGS) biosynthetic gene cluster in Streptomyces platensis NRRL 18993 contains 11 genes.
- This cluster includes an acyltransferase (AT)-less type I polyketide synthase (PKS) and three tailoring enzymes (MgsIJK).
Purpose of the Study:
- To investigate the novel products generated by the AT-less type I PKS.
- To elucidate the function of the MgsIJK tailoring enzymes in iso-MGS biosynthesis.
- To understand the substrate promiscuity of the tailoring enzymes.
Main Methods:
- Systematic gene inactivation of mgsIJK in Streptomyces platensis.
- Analysis of biosynthetic products from engineered strains.
Main Results:
- Two novel products from the AT-less type I PKS were identified, revealing a new characteristic for this enzyme class.
- The functions of MgsIJK enzymes were clarified, accounting for all known post-PKS biosynthetic intermediates.
- Significant substrate promiscuities were observed for the MgsIJK tailoring enzymes.
Conclusions:
- The study reveals a novel feature of AT-less type I PKSs in producing multiple nascent products.
- The MgsIJK enzymes play crucial roles in iso-MGS biosynthesis, exhibiting broad substrate specificity.
- This work deepens the understanding of complex polyketide biosynthesis pathways.
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