Structure, function, and engineering of plant polyketide synthases

Area of Science:

• Biochemistry and Molecular Biology
• Enzymology
• Natural Product Synthesis

Background:

• Type III polyketide synthases (PKSs) are crucial enzymes that synthesize diverse polyketide scaffolds.
• These enzymes share conserved structural features, including a thiolase fold and a catalytic triad.
• Functional diversity arises from subtle variations in active site architecture.

Purpose of the Study:

• To detail methods for identifying, characterizing, and engineering Type III PKSs.
• To provide an overview of the structures and functions of these enzymes.
• To highlight the potential for structure-guided enzyme engineering.

Main Methods:

• Biochemical characterization of Type III PKSs.
• Structural analysis of enzyme active sites.
• Structure-guided enzyme engineering approaches.

Main Results:

• Subtle active site differences dictate functional diversity in highly homologous Type III PKSs.
• Detailed understanding of catalytic mechanisms and versatility.
• Established platform for generating novel polyketides through enzyme engineering.

Conclusions:

• Knowledge of Type III PKS structure-function relationships facilitates enzyme engineering.
• Structure-guided approaches enable the creation of unnatural polyketides.
• Type III PKSs represent valuable targets for synthetic biology and drug discovery.