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Updated: May 30, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
The stereochemistry of complex polyketide biosynthesis by modular polyketide synthases
1Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. dkwan@chem.ubc.ca
This review details the stereochemistry of polyketide biosynthesis by modular polyketide synthases (PKSs). It covers how these enzymes control the precise arrangement of atoms in medically important natural products.
Area of Science:
- Biochemistry
- Natural Product Synthesis
- Enzymology
Background:
- Polyketides are vital natural products synthesized by polyketide synthases (PKSs), mimicking fatty acid biosynthesis.
- Modular PKSs assemble polyketide chains via enzyme-bound intermediates, using activated acyl-CoA precursors.
Purpose of the Study:
- To review studies determining the stereochemistry of reactions in modular polyketide synthase biosynthesis.
- To highlight the generation of stereochemical diversity in polyketide structures.
Main Methods:
- Analysis of stereochemical outcomes from ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) activities.
- Examination of stereochemistry influenced by acyltransferase (AT) and ketosynthase (KS) domains.
Main Results:
- PKS enzymatic activities dictate the stereochemistry of hydroxyl groups and double bonds (cis/trans).
- Use of propionate extender units introduces branching methyl groups with specific chirality.
- Stereochemical diversity arises from the combination and action of different enzymatic modules and domains.
Conclusions:
- Understanding PKS stereochemical control is crucial for synthesizing complex polyketides.
- The modular nature of PKS allows for predictable, yet diverse, stereochemical outcomes.
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