Functional analysis of radical SAM enzymes involved in the biosynthesis of aminoglycoside antibiotics

2016 Fiscal Year Final Research Report

• Project/Area Number: 26410174
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KUDO FUMITAKA 東京工業大学, 理学院, 准教授 (00361783)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 天然物化学 / 生合成 / 酵素 / アミノグリコシド抗生物質 / ネオマイシン / アプラマイシン / ラジカルSAM酵素 / 鉄硫黄クラスター

Outline of Final Research Achievements

Aminoglycoside antibiotics contain a unique aminocyclitol that is decorated with various aminosugars leading to a wide variety of structures including kanamycin and neomycin. A common biosynthetic scheme of kanamycin and neomycin has been elucidated, when this project started. Thus, unique enzymatic modifications of common biosynthetic intermediates were speculated to be involved in the individual biosynthetic machinery. Radical S-adenosyl-L-methionine (SAM) enzymes that are often encoded in the biosynthetic gene clusters are supposed to be responsible for such unique reaction, because radical SAM enzyme generates 5′-deoxyadenosyl radical that can trigger various radical reactions in living system. In current research program, I focused on the functional analysis of radical SAM epimerase NeoN in neomycin B biosynthesis and radical SAM dehydratase AprD4 in apramycin biosynthesis. Consequently, we could clarify the functions of NeoN and AprD4 and propose plausible reaction mechanisms.

Free Research Field

生物有機化学