Characterization of Catalytic Diversity in Megaenzyme Systems

. 细菌和真菌产生广泛的次级代谢产物。这些天然化学物质使微生物具有生长优势或杀死竞争生物。这些化合物的生物活性也使它们作为农业试剂、杀虫剂和“绿色”化学品对社会有用。许多负责合成这些次级代谢产物的蛋白质构成称为聚酮酶和非核糖体肽合成酶的大型复杂酶系统（巨酶或巨合成酶）。典型的大合成酶由特定结构域的重复组合形成，并从单体结构单元产生各种小分子化合物。有趣的是，在一些系统中，通过从各种其他细胞过程中挑选蛋白质、蛋白质结构域和/或底物来进一步增加多样性。这项研究计划的目标是调查和结构表征megaenzyme系统，显示非典型的组成和机制，导致这些新的组件。

. 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.