Functional and structural analyses of iterative type I polypektide synthases

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H03995
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Kitasato University (2021); Iwate Medical University (2017-2020)
• Principal Investigator: Fujii Isao 北里大学, 薬学部, 客員教授 (70181302)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: ポリケタイド / ポリケタイド合成酵素 / 生合成

Outline of Final Research Achievements

As a part of studies on fungal iterative type I polyketide synthases (iPKSs) to elucidate their reaction control mechanisms, the biosynthetic gene cluster of shimlactone was cloned from Emericella variecolor GF10 and analyzed. Although it was difficult to express ShmA protein in yeast, ShmA protein with His-tag was well expressed in Aspergillus oryzae and successfully purified using Ni-affinity chromatography. Thus obtained homogeneous ShmA iPKS protein paves the way to further studies on its three dimensional structural elucidation as an example of fungal iPKS.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

糸状菌は様々なポリケタイド化合物を生産し、重要な医薬供給源となっている。本研究では、神経突起生成活性を有し特異なビシクロ環構造をもつシマラクトンについて、ポリケタイド合成酵素ShmAを含むシマラクトン生合成遺伝子クラスターを同定するとともにShmAタンパクの異種発現、精製法を確立した。これは今後のポリケタイド合成酵素を利用した生物合成系開発への足掛かりとなるものと考えられる。