Extensive Alanine Scanning of Loop Regions in Ketosynthase Domains Identifies Non-Active Site Mutations with Drastic Effects on Polyketide Biosynthesis.

Abstract excerpt

Modular polyketide synthases (PKSs) produce diverse natural products with significant pharmaceutical value, but their protein engineering for drug discovery is hampered by the unpredictable substrate specificity of their ketosynthase (KS) domains. While previous studies have focused on the KS active sites, we conducted extensive alanine scanning of loop regions of a KS domain, most of which are distant from the...

Topics

• Polyketide Synthases
• Catalytic Domain
• Alanine
• Polyketides
• Mutation
• Models, Molecular
• Substrate Specificity
• Protein Domains
• Mutagenesis, Site-Directed