Stepwise cyclopropanation on the polycyclopropanated polyketide formation in jawsamycin biosynthesis
Tomoshige Hiratsuka1, Hideaki Suzuki1, Atsushi Minami1
1Division of chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan. hoik@sci.hokudai.ac.jp.
Organic & Biomolecular Chemistry
|January 7, 2017
Summary
Researchers uncovered a novel stepwise mechanism for jawsamycin biosynthesis, involving a unique polycyclopropane structure. This discovery sheds light on the intricate enzymatic regulation of polyketide synthesis.
Area of Science:
- Biochemistry
- Organic Chemistry
- Molecular Biology
Background:
- Jawsamycin is a complex polyketide-nucleoside hybrid.
- It features a distinctive polycyclopropane moiety within its polyketide chain.
Purpose of the Study:
- To elucidate the biosynthetic pathway of jawsamycin.
- To propose a mechanism for the enzymatic synthesis of its unique polycyclopropane structure.
Main Methods:
- Isolation and characterization of jawsamycin analogs.
- Analysis of cyclopropane-deficient mutants.
- Hypothesis of a stepwise cyclopropanation mechanism.
Main Results:
- Discovery of jawsamycin analogs lacking the characteristic cyclopropane rings.
- Proposal of a sequential enzymatic cyclopropanation pathway.
- Identification of a regulatory balance between condensation and cyclopropanation reaction rates.
Conclusions:
- The biosynthesis of jawsamycin proceeds through a stepwise cyclopropanation mechanism.
- Enzymatic control over reaction rates is crucial for forming the polycyclopropane moiety.
- This study provides insights into the enzymatic synthesis of complex polycyclic structures.
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