Pentabromopseudilin (PBP) is a polybrominated pyrrole alkaloid isolated from marine bacteria Pseudoalteromonas. It has been found to have anti-myosin activities that could be exploited for cancer therapy and it also has sub-micromolar activity against methicillin-resistant Staphylococcus aureus (MRSA). Isolated along with PBP from Pseudoalteromonas, 3,5,7-tetrabromobenzofuro[3,2-b]pyrrole (BFP) is also active against MRSA and it features a tricyclic structural scaffold that is putatively a result of phenolic cyclization onto the pyrrole ring in PBP. It is not yet known whether this product, BFP, is made naturally due to an enzymatic reaction with PBP or if it is a degradation product of PBP. The overarching goal of this project is to engineer a cytochrome P450 enzyme through random chemical mutagenesis in order to successfully catalyze the conversion of PBP to BFP. Development of this methodology will also allow the synthesis of other bioactive natural products that require a similar bond formation on a labile pyrrole ring. Herein reported are our efforts and progress in the engineering of the cytochrome P450 enzyme.

Engineering of cytochrome P450 enzyme towards marine natural product total synthesis

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.