The molecular architecture and regulation of the PDH-ODH hybrid complex

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05803
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38020:Applied microbiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kosono Saori 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (90321760)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 2-オキソ酸デヒドロゲナーゼ複合体 / PDH / ODH / Corynebacterium / リジンアセチル化 / グルタミン酸生産

Outline of Final Research Achievements

Pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase (ODH) from Corynebacterium glutamicum exist as a unique hybrid complex in which CgE1p and CgE1o simultaneously associate with the CgE2-CgE3 subcomplex. In this study, we have elucidated the molecular structure of the hybrid complex, including the subunit composition. In vivo and in vitro studies revealed that the hybrid complex has a compact size compared to PDH and ODH from E. coli. In addition, the existence of mechanisms that flexibly regulate PDH and ODH activities, including differences in the binding affinities of the two E1 subunits for the CgE2 subunit, acetylation of the CgE2-PSBD domain, and CgE1o multimerization, was suggested.

Free Research Field

応用微生物学

Academic Significance and Societal Importance of the Research Achievements

Corynebacterium glutamicumにおけるユニークなPDH-ODHハイブリッド複合体の分子構造基盤を初めて詳細に明らかにした。また、2つのE1サブユニットのCgE2への結合親和性の違いや、CgE2-PSBDドメインのアセチル化、CgE1o多量体形成など、PDHおよびODH活性を柔軟に調節する機構の一端を明らかにした。PDHおよびODH活性調節は中心炭素代謝フロー制御に重要な役割を持つため、これらの成果はC. glutamicumを用いた有用物質生産の代謝デザインに重要な知見となることが期待される。