Our latest manuscript about malayamycin biosynthesis was published in ACS Chemical Biology

This manuscript highlights the achievements of Matthew with significant help by Jib and Yanan and describes our successful characterization of the biosynthesis of malayamycin A, a unique C6-sugar nucleoside antifungal.  The study revealed that the biosynthesis proceeds through cryptic phosphorylation analogous to that in nikkomycin and polyoxin.  The study also revealed a divergent biosynthesis of high-carbon sugar nucleoside natural products, their evolutional relationships, and the potential for future genome mining discovery. 

Haoran received 2021-2022 Chancellor’s Award for Research Excellence (CARE)

Haoran was selected as a recipient of 2021-2022 Chancellor’s Award for Research Excellence (CARE). His research project focuses on the mechanism of MoaA radical SAM enzyme in the molybdenum cofactor (Moco) biosynthesis and  Moco deficiency disease (MoCD) in humans. Parts of his achievements have already been published in JACS (in 2020 and 2021). Haoran’s achievements have broad scientific and translational impacts as they provided unprecedented insights into the mechanism of enzyme-catalyzed radical reactions and significant implications in the future development of MoCD therapeutics. Congratulations, Haoran!!

Haoran’s paper is published in JACS.

Haoran’s paper about the catalytic function of the auxiliary cluster of MoaA is now published online on JACS.  In this work we determined the reduction potentials of the two 4Fe-4S clusters in MoaA and compared them with theoretical reduction potentials of the putative aminyl radical intermediate. The results suggested PCET mechanism for the aminyl radical reduction. Furthermore, the EPR characterization of the C4′ radical revealed an electronic coupling between GTP and the auxiliary cluster, suggesting a potentially missing mechanism of catalysis.

Matthew and Jib’s paper is published in Biochemistry

This paper characterizes the amide ligases in peptidyl nucleoside antifungal biosynthesis and demonstrates that the cryptic phosphorylation retains until the last step of these pathways. Cryptic phosphorylation is a mechanism recently identified in these pathways and emerging in other nucleoside and aminoglycoside pathways. The results provide further insights into the crytpic phosphorylation in natural product biosynthesis in general.

Haoran won the best poster award in Southeast Enzymes Conference

Haoran received the best poster award in the 11th Annual Southeast Enzymes Conference (SEC) held virtually in April. He presented his work on the mechanism of MoaA radical SAM enzyme catalysis. He combined enzyme kinetics, EPR, and DFT calculation to obtain insights into the mechanism of rate acceleration of MoaA-catalyzed radical C-C bond formation. A part of his work was published in JACS in 2020. Congratulations, Haoran.

Abhi’s protocol paper on glucan synthase assay is published online

In this protocol paper, we describe details of the GS assay protocol that we originally published in the 2020 Biochemistry paper.  The assay is based on size-exclusion chromatography under the basic condition that 1,3-beta-D-glucan is soluble. This approach allows quantitative determination of the amount and the length of glucan produced by yeast GS. In our Biochemistry 2020 paper, we used this assay to study the mechanism of GS catalysis and inhibition.

Matthew successfully defended his PhD dissertation

Matthew successfully defended his Ph.D. dissertation about the mechanism of peptidyl nucleoside antifungal antibiotic biosynthesis. He discovered cryptic phosphorylation during the PN biosynthesis and characterized all the downstream enzymes in the pathway. He also demonstrated the generality of this cryptic phosphorylation in other antifungal nucleoside pathways. Please see his NCB paper for details. Congratulations!!