Probing the Substrate Specificity of Polyketide Synthase

描述：（由申请人提供）聚酮化合物是一个大家族 结构多样且复杂的天然产物，具有广泛的用途 生物学功能。在自然界中，聚酮化合物是通过大量生物合成的 聚酮合酶（PKS）通过连续缩合 简单的单体。拟议研究的长期目标是了解 PKS以通过生物工程生成新型聚酮化合物 技术。对于模块化 PKS，每个单独的模块都包含所有必要的 活性位点进行一轮合成。拟议的研究将 表达和纯化 6 脱氧赤酮内酯 B 合酶的各个模块 （DEBS）。 DEBS 是一种模块化 PKS，负责生物合成 抗生素红霉素。基板专门设计用于探测 不同基质的结合和处理的基本规则 单独的模块。天然和混合双模块结构也将是 准备并接受新型底物以了解掺入情况 基板由第一模块传送至第二模块以进行 进一步的化学转化。了解底物的特殊性 PKS是迈向多种组合生物合成的重要一步 聚酮化合物。

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.