DISSECTING AN ANTIBIOTIC FACTORY: OBTAINING THE STRUCTURE OF A POLYKETIDE SYNTHA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 聚酮合成酶可合成多种药物，包括抗癌药物、免疫抑制剂和抗生素。合成酶是多酶装配线，可以分解成称为模块的酶簇，这些模块催化增加小的碳构建块，生长碳链。我们正在试图理解一个模块的结构和原子分辨率下催化的细节。只有到那时，我们才能假设催化是如何实现的，包括实现特异性和立体选择性的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polyketide synthases synthesize a wide variety of pharmaceuticals including anti-cancer agents, immunosuppressants, and antibiotics. The synthases are multienzyme assembly line that can be broken down into clusters of enzymes called modules that catalyze the addition of small carbon building blocks growing carbon chains. We are trying to understand the architecture of a module and the details of catalysis at atomic resolution. Only then will we be able to hypothesize how catalysis is achieved, including the mechanisms enabling specificity and stereoselectivity.