Module-Module Linking Scheme of Polyketide Synthases

描述（由申请人提供）：聚酮合酶（PKS）是负责产生许多具有医学意义的聚酮化合物（如抗生素红霉素和抗肿瘤化合物埃博霉素）的大模块酶。PKS的每个模块具有其自身的用于延长和化学修饰聚酮化合物链的自含催化机构。大自然合成精细的聚酮化合物是通过将各个PKS模块（每个模块都有自己的催化功能）以流水线的形式连接在一起。该提案旨在利用PKS的模块化排列，希望合成和发现新的医学有益的化合物。本提案的目标是开发一种体外系统，用于单个PKS模块的轻松重排和重组。连接各个PKS模块而不破坏其天然功能的能力为生产和最终筛选PKS的大型组合文库提供了机会，每个组合文库都具有生产新型聚酮化合物的潜力。

DESCRIPTION (provided by applicant): Polyketide Synthases (PKSs) are large modular enzymes responsible for the production of numerous medically significant polyketides such as the antibiotic Erythromycin and the antitumor compound Epothilone. Each module of a PKS has its own self-contained catalytic machinery for elongating and chemically modifying a polyketide chain. Nature synthesizes elaborate polyketides by linking together individual PKS modules (each with its own catalytic function) in an assembly-line format. This proposal aims to take advantage of the modular arrangement of PKSs with the hope of synthesizing and discovering novel medically beneficial compounds. The goal of this proposal is to develop an in vitro system for the facile rearrangement and recombination of individual PKS modules. The ability to connect individual PKS modules, without disrupting their natural functions, presents the opportunity for the production and eventual screening of large combinatorial libraries of PKSs, each having the potential to produce novel polyketide compounds.