[대학원 생명과학과 세미나 안내]
연사 : 성광훈 박사(Helmholtz Centre for Infection Research)
연제 : Insights into the dual activity of a DH domain asdehydratase and cyclase in ambruticin biosynthesis
일시 : 2017년 4월 20일 (목) 오전 10시 40분
장소 : 하나과학관 A동 207호
초청교수 : 송현규 교수
Abstract
Oxygen-containing heterocycles are a common structuralmotif of polyketide natural products and contribute significantly to theirbiological activity, but studies on the enzymatic mechanism of cyclasesinstalling these moieties are still owing. Here, we report structural andmechanistic investigations on AmbDH3, a polyketide synthase domain with dualactivity as dehydratase (DH) and pyran-forming cyclase in ambrucitinbiosynthesis. AmbDH3 is similar to monofunctional DH domains, using His51 andAsp215 for dehydration. Val173 was identified as essential for cyclisation andthus dual activity, which was confirmed in biochemical experiments withsynthetic substrate surrogates. This is the first structural analysis of a PKSdomain with an activity as a pyran-forming cyclase. Our results pave the wayfor a sequence-based search for similar cyclase domains and also openinteresting prospects for the generation of new pyran-containing naturalproduct derivatives by combinatorial biosynthesis.