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

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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.