Characterization of Catalytic Diversity in Megaenzyme Systems

。细菌和真菌产生广泛的次生代谢产物。这些天然化学物质给微生物带来生长优势，或者杀死竞争对手的有机体。这些化合物的生物活性也使它们成为对社会有用的农用制剂、杀虫剂和“绿色”化学品。许多负责合成这些次级代谢物的蛋白质组成了大型、复杂的酶系统(巨酶或巨合酶)，称为聚酮合成酶和非核糖体多肽合成酶。典型的巨合酶是由特定结构域的重复组合形成的，并从单体构建块产生各种小分子化合物。有趣的是，在一些系统中，通过加入来自各种其他细胞过程的蛋白质、蛋白结构域和/或底物，进一步增加了多样性。这项研究计划的目标是调查和结构表征巨型酶系统，这些系统表现出非典型的组成和机制，由这些新的成分所导致。

. Bacteria and fungi produce a wide range of secondary metabolites. These natural chemicals give microbes growth advantages or kill competing organisms. The biological activities of these compounds also make them useful to society as agricultural agents, pesticides and "green" chemicals. Many of the proteins responsible for synthesis of these secondary metabolites constitute large, complex enzyme systems (megaenzymes or megasynthases) called polyketide synthases and nonribosomal peptide synthetases. Canonical megasynthases are formed of repeating combinations of specific domains, and produce a variety of small molecule compounds from monomer building blocks. Intriguingly, in some systems, the diversity is further increased by co-opting proteins, protein domains, and/or substrates from various other cellular processes. The goal of this research program is to investigate and structurally characterize megaenzyme systems that display atypical composition and mechanisms resulting from the inclusion of these novel components.