Engineering of type III polyketide synthase by deletion and addition of residues

2015 Fiscal Year Final Research Report

• Project/Area Number: 26560435
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: University of Toyama
• Principal Investigator: MORITA HIROYUKI 富山大学, 和漢医薬学総合研究所, 教授 (20416663)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 酵素工学 / ポリケタイド合成酵素 / X線結晶構造解析

Outline of Final Research Achievements

In order to modify the function of type III polyketide synthase, we carried out deletion mutagenesis studies on octaketide synthase (OKS), which catalyzes sequential condensations of eight molecules of malonyl-CoA to produce SEK4/SEK4b. The deletion mutagenesis studies revealed that the loss of Varine351, lining the active site cavity of OKS, results in specializing its starter substrate specificity in fatty acyl CoAs. Furthermore, a crystal structure analysis of the mutant enzyme suggested that an expansion of the active-site cavity near catalytic residue, cysteine, specialized the substrate specificity of the mutant in the fatty acyl CoAs.

Free Research Field

天然物化学