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!!
Our perspective on MoaA and MoaC is published in ACS Bio Med Chem Au
In this perspective, we summarized the role of Moco in humans and pathogenic bacteria and the recent progress on the functional and mechanistic characterization of MoaA and MoaC. We also highlighted key unsolved questions in the field, especially in the context of human disease. We hope this perspective will foster the progress of the field.
Haoran’s paper is highlighted in JACS Spotlight
Haoran’s paper about the redox function of the auxiliary cluster in MoaA was highlighted in the JACS spotlight. See the earlier post for the details of the work.
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.
Lydia joined the lab
Lydia Li, a first-year biochemistry student, joined our lab. She will be working on the Moco project. Welcome, Lydia!
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!!
Matthew and Jib’s work is published online in Nature Chemical Biology
In this paper, we report the discovery of cryptic phosphorylation essential for the biosynthesis of nikkomycin and polyoxin class of antifungal peptidyl nucleoside natural products. Nikkomycins and polyoxins are an important class of antifungals currently used as agricultural fungicides and are clinically investigated to treat invasive fungal infections in humans. However, their biosynthesis has long remained poorly characterized. Our discovery of the cryptic phosphorylation allowed the characterization of all the downstream steps in these pathways and revealed a divergent mechanism of structurally related antifungal nucleosides. Furthermore, our study suggests that the cryptic phosphorylation is conserved in many other nucleoside biosynthetic pathways. Congratulations, Matthew and Jib!
