Tolerance and specificity of polyketide synthases
C Khosla1, R S Gokhale, J R Jacobsen
1Department of Chemical Engineering, Stanford University, California 94305-5025, USA. ck@chemeng.Stanford.edu
Annual Review of Biochemistry
|June 29, 2000
Summary
Polyketide synthases build complex molecules like fatty acids. Understanding their molecular recognition is key to engineering new compounds through combinatorial manipulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Natural Product Synthesis
Background:
- Polyketide synthases (PKS) assemble complex natural products via decarboxylative condensations, similar to fatty acid biosynthesis.
- Unlike fatty acids, PKS intermediates undergo variable processing, leading to diverse functional groups, chiral centers, and cyclizations.
- The modularity of PKS suggests potential for pathway reprogramming via combinatorial manipulation.
Purpose of the Study:
- To review recent genetic, biochemical, and chemical investigations into polyketide synthase (PKS) tolerance and specificity.
- To explore the molecular recognition features of different polyketide synthases.
- To discuss the implications of these findings for biosynthetic engineering.
Main Methods:
- Genetic investigations of PKS pathways.
- Biochemical studies of PKS enzyme activity and substrate specificity.
- Chemical analyses of polyketide products and intermediates.
Main Results:
- Insights into the substrate tolerance and specificity of various polyketide synthases.
- Characterization of molecular recognition mechanisms within PKS active sites.
- Demonstration of structural and functional modularity in PKS systems.
Conclusions:
- A deeper understanding of PKS molecular recognition is crucial for harnessing their biosynthetic potential.
- Recent studies provide valuable insights into PKS specificity and tolerance.
- These findings pave the way for rational reprogramming of polyketide biosynthesis for engineering purposes.
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