Probing the Substrate Specificity of Polyketide Synthase

描述：(申请人提供)多酮类化合物是一大类 结构多样和复杂的天然产品，具有广泛的 生物功能。在自然界中，聚酮类化合物是由大量的 聚酮合成酶(PKS)通过连续缩合 简单的单体。这项拟议研究的长期目标是了解 通过生物工程产生新型聚酮的PKSS 技巧。对于模块化PKS，每个单独的模块包含所有必需的 活性部位进行一轮合成。拟议的研究将 6-脱氧赤藓内酯B合酶各个模块的表达和纯化 (Debs)。Debs是一个模块化的PKS，负责生物合成 抗生素红霉素。衬底被设计成专门探测 不同底物的结合和加工的基本规则 单独的模块。本地和混合双模结构也将是 制备并受制于新型底物以了解掺入 并传送到第二模块，以便 进一步的化学变化。了解底物的特性 PKS是迈向多种生物合成的重要一步 聚酮类化合物。

DESCRIPTION: (provided by applicant) Polyketides are a large family of structurally diverse and complex natural products with a wide range of biological functions. In nature, polyketides are biosynthesized by large polyketide synthase enzymes (PKS) through the successive condensations of simple monomers. The long-term goal of the proposed research is to understand the PKSs in order to generate novel polyketides through bioengineering techniques. For modular PKS, each individual module contains all the necessary active sites to carry on one round of synthesis. The proposed research will express and purify the individual modules of 6 deoxyerythronolide B synthase (DEBS). DEBS is a modular PKS responsible for the biosynthesis of the antibiotic erythromycin. Substrates are designed to specifically probe the underlying rules for binding and processing of different substrates by the individual modules. Native and hybrid bimodular constructs will also be prepared and subjected to the novel substrates to understand the incorporation of the substrates by the first module and transfer to the second module for further chemical transformations. Understanding the substrate specificities of the PKS is an important step towards combinatorial biosynthesis of diverse polyketides.