[대학원 생명과학과 세미나 안내]
연사 : 김석희 교수(서울대학교 화학부)
연제 : Natural diversity and biosynthesis of multicyclic peptides carrying macrolactone linkages
일시 : 2021년 11월 19일 (금) 오후 5시
장소 : 온라인 화상 강의로 진행됩니다.
초청교수 : 송현규 교수
Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large class of natural products that present diverse structures and biological functions. Unlike non-ribosomal peptides, they are initially synthesized as a precursor peptide by ribosome and subsequently modified by modification enzymes. This simple biosynthetic pathway of RiPPs underlies the high potential for engineering new peptide-based functional molecules and therapeutics. Members of the microviridin family of RiPPs contain the distinct -ester or -amide macrocycles that connect a side-chain carboxylic acid of glutamate or aspartate to a side-chain hydroxyl or amine group of threonine, serine, or lysine. Although these side-to-side cross-links may generate topologically diverse macrocyclic structures, microviridins have shown only a single tricyclic structure with a highly-conserved core motif.
Using genome mining and structural characterization, we identified several new groups of microviridin-like RiPPs with novel consensus core sequence and ring structure. They show variations in the size and number of -ester/amide linkages, and present distinct topologies of bi-, tri-, or penta-cyclic peptides. Because they all contain at least one -ester bond, we named the an expanded RiPP family as omega-ester containing peptides (OEPs). We also showed that the the cross-reactivity of enzymes that belong to different OEP sub-groups is determined by enzyme as well as by core sequence. This result led us to design and synthesize multi-functional hybrid RiPPs by combinatorial application of multiple orthogonal enzyme-substrate pairs. We also obtained multiple crystal structures of the macrocyclase enzyme in complex with substrates, and demonstrated that the ring-forming carboxylate is recognized by a highly conserved arginine residue in enzyme. Collectively, we demonstrate that the microviridin-like RiPPs have much higher natural diversity in structure and present a great potential for the synthetic biology application to find novel bioactive peptides.