Catalytic mechanism of radical SAM enzyme PqqE in pyrroloquinoline quinone biosynthesis

Wen Zhu¹, Anthony T. Iavarone², and Judith P. Klinman^2,3

1Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306
2California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720
3Department of Chemistry, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

Pyrroloquinoline quinone (PQQ) is a bacterial peptide-derived redox cofactor that has been shown to be beneficial to humans as a nutraceutical. The details of the catalytic process involved in the biological origin of PQQ have just started to unfold. In the first step of PQQ biosynthesis, a de novo carbon-carbon bond is installed on a precursor peptide, PqqA, by the radical SAM enzyme PqqE, in complex with the peptide chaperone PqqD and SAM. How the protein environment and the multiple iron-sulfur clusters in PqqE facilitate the challenging radical chemistry remains unclear. I will present a biochemical and biophysical characterization of PqqE in complex with its substrates and chaperone protein. Our structure-function analysis of the protein complex suggests that the cooperative contribution from the cofactor-protein and protein-protein interactions in the quaternary enzyme-substrate complex modulates the catalysis of PqqE in the initiation step of PQQ biogenesis.