Investigation of Cytochrome P450 Enzymes as Biocatalysts for Multifunctional C-H Oxidation; and a Case Study of a Graduate/Undergraduate Laboratory Exchange Program

[摘要] Cytochrome P450 monooxygenases are ubiquitous in nature, catalyzing a variety of oxidative transformations.Recent work has shown that the bacterial P450 PikC can catalyze the regioselective hydroxylation of both small molecule and larger macrolactone ring systems via a unique anchoring mechanism.The catalytic versatility of PikC, however, remains limited primarily to hydroxylation reactions.Further research into the activity of mixed function P450s could therefore expand upon the use of enzymes as biocatalysts.Chapters 1-3 of this thesis focus on the rapid synthesis of a series of analogs of tirandamycin, the natural substrate of the multi-functional P450 TamI, to access novel oxidation products using either PikC or TamI.Investigation into these biocatalytic systems explores whether PikC can install multiple types of oxidative functionality within the bicyclic core of tirandamycin as well as probes the utility of TamI as a mixed function biocatalyst for site-selective oxidation of unnatural substrates.Chapter 4 of this thesis describes a case study of a laboratory exchange between a chemistry graduate student from a R1 research institution and an undergraduate student involved in summer research at a primarily undergraduate institution (PUI).Interviews and observations were used as a means to document learning of participants.Findings from this study show an increase in personal and professional growth among exchange students and provide support for the design and implementation of these programs by others.

[发布机构] University of Michigan

[效力级别] Tirandamycin

[关键词] Cytochrome P450;Tirandamycin;C-H Functionalization;Laboratory Exchange Program;Chemistry;Science;Chemistry