Post-Polyketide Synthase Steps in Iso-migrastatin Biosynthesis, Featuring Tailoring Enzymes with Broad Substrate Specificity

2013/02/08 by Ming Ma, Thomas Kwong, Si‐Kyu Lim +3 · 1 citation
Medicine · Chemistry · Biochemistry, Genetics and Molecular Biology · #Microbial Natural Products and Biosynthesis #Synthetic Organic Chemistry Methods #Marine Sponges and Natural Products

paper · doi:10.1021/ja4002635

openalex publication_date 2013/02/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/24

Abstract

The iso-migrastatin (iso-MGS) biosynthetic gene cluster from Streptomyces platensis NRRL 18993 consists of 11 genes, featuring an acyltransferase (AT)-less type I polyketide synthase (PKS) and three tailoring enzymes MgsIJK. Systematic inactivation of mgsIJK in S. platensis enabled us to (i) identify two nascent products of the iso-MGS AT-less type I PKS, establishing an unprecedented novel feature for AT-less type I PKSs, and (ii) account for the formation of all known post-PKS biosynthetic intermediates generated by the three tailoring enzymes MgsIJK, which possessed significant substrate promiscuities.

Citations

• Diverted Total Synthesis Leads to the Generation of Promising Cell-Migration Inhibitors for Treatment of Tumor Metastasis: In vivo and Mechanistic Studies on the Migrastatin Core Ether Analog
• Emergence of potent inhibitors of metastasis in lung cancer via syntheses based on migrastatin

Cited by

• Isomigrastatin [wikipedia]