Generation of unnatural amino acids using enzymes for the biosynthesis of antitubercular antibiotic D-cycloserine

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07997
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Hiroshima University
• Principal Investigator: Matoba Yasuyuki 広島大学, 医歯薬保健学研究科(薬), 准教授 (90363051)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 抗生物質 / 微生物薬品学 / 構造生物学 / 酵素

Outline of Final Research Achievements

Our group has recently cloned a gene cluster containing the biosynthetic genes for an antituberculosis antibiotic, D-cycloserine (D-CS) from D-CS-producing Streptomyces lavendulae. The aim of this study is to generate unnatural amino acids by using the enzymes in the D-CS-biosynthetic pathway. Based on the crystal structures of DcsD and DcsG, previously determined by us, mutational analyses were performed to identify the important residues for the catalytic activity and the substrate preference. In addition, crystal structure of DcsA was determined using the single anomalous dispersion method. Catalytic mechanism of DcsA was proposed based on the structural, mutational, and resonance Raman spectroscopic analyses.

Free Research Field

医歯薬学