Author: Bach Nguyen

Ken gave a beautiful seminar at Duke Chemistry, drawing a great turnout from both students and faculty. He shared the story of our lab’s mechanistic studies of MoaA and MoaC, two essential enzymes that catalyze the remarkable transformation of GTP into the core scaffold of the molybdenum cofactor during the first steps of its biosynthesis. This work reflects years of collaborative effort with colleagues across the university. It was also driven by several amazing graduate student alumni—Brad, Edward, Haoran, and Lydia—whose work helped uncover the fascinating chemistry behind this complex biosynthetic pathway.

Ken gave a beautiful seminar at Duke Biochemistry, drawing attendees from across campus. He highlighted the outstanding science produced by many current and former lab members over the past ~15 years, with work published in leading journals.

Bach has been awarded the competitive Katherine Goodman Stern Fellowship from Duke Graduate School. Supported by a generous endowment established by Katherine Stern, the fellowship provides an annual stipend as well as coverage of tuition and mandatory fees to exceptional advanced PhD students who are in the write-up stage of their dissertations. This award recognizes Bach’s outstanding academic and research accomplishments. Congrats, Bach!

In this new study published in PNAS, Haoran and Lydia, together with collaborators in the Weitao Yang and Pei Zhou labs at Duke and the Alexey Silakov lab at Penn State, uncovered a substrate-triggered radical initiation. Using radical SAM enzyme MoA as a model, they discovered that MoaA uses its conformationally flexible C-terminal tail with two conserved Gly residues (GG motif) at the C-terminus as a sensor to detect substrate guanosine 5′-triphosphate (GTP) binding and trigger reductive SAM cleavage. Importantly, they also found that mutations disrupting this regulatory mechanism lead to Moco deficiency disease in humans. Congratulations to Haoran and Lydia!

Brycen received a poster award at the Biochemistry Department’s annual retreat for his presentation on Yanan’s work and his rotation research into the functional characterization of novel HDO enzymes. Congratulations, Brycen!

In this study, we demonstrate that PolF, a member of the haem-oxygenase-like dimetal oxidase/oxygenase (HDO) superfamily, catalyzes the conversion of L-isoleucine (L-Ile) and L-valine into their azetidine derivatives via a 3,4-desaturated intermediate. Mechanistic analyses reveal that a μ-peroxo-Fe(III)₂ ​ intermediate mediates the cleavage of unactivated C–H bonds, while subsequent reactions—including C–N bond formation—likely proceed through radical pathways. Additionally, we identify PolE, a DUF6421 family enzyme, as an Fe- and pterin-dependent oxidase that promotes L-Ile desaturation, thereby enhancing substrate flux for PolF. Collectively, these findings shed light on azetidine biosynthesis and expand our understanding of HDO enzyme catalysis. The significance of our work was also highlighted in the news section of the School of Medicine.

In this work, Bach uncovered a novel mechanism used by radical SAM enzyme DynA to catalyze the cross-linking in dynobactin biosynthesis. Specifically, DynA utlizes a radical-mediated nucleophilic mechanism for the unprecedented C-N cross-link through a p-quinone methide intermediate. This quinone methide-dependent mechanism of RiPPs cross-linking is distinct from the previously reported RiPPs cross-linking mechanisms and represents a novel mechanism in RiPPs biosynthesis. Congrats, Bach!