News

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!

Bach received a poster award during the Biochemistry Department’s annual retreat. He presented his discovery of a novel mechanism of the radical SAM enzyme DynA in catalyzing post-translational crosslinking in dynobactin biosynthesis. Congratulations, Bach!

We moved to a new space within the Nanaline Duke building.  More unified and less compartmentalized space.  It was quite a bit of effort but well worth it. Well done, everyone!

A graduate student, Bach Nguyen, is awarded the prestigious predoctoral fellowship from the American Heart Association (AHA). His proposed project aims to study the functions and mechanisms of enzymes responsible for the biosynthesis of peptide antibiotics that selectively kill Gram-negative pathogens, whose infections could lead to severe complications and devastating consequences on the cardiovascular system. Congratulations, Bach!

Many nucleoside antibiotics and antifungals are biosynthesized through divergent mechanisms. This concept paper reviews the recent developments in our understanding of their biosynthesis and discusses the potential for genome-mining discovery of novel nucleoside antibiotics and antifungals based on a thorough analysis of the genome sequence information.  This paper is a part of the Next Generation of Chemical Biology issue.

Bach received a fellowship from the Triangle Center of Evolutional Medicine to study the natural evolution of naturally-occurring peptide antibiotics.  While >60% of FDA-approved antibiotics originate from Nature, how these antibiotics evolved is largely unexplored.  In this project, Bach will study the evolutional course of antibiotics using the recently discovered ribosomally synthesized and posttranslationally modified peptides (RiPPs) antibiotics.  The results will provide novel insights into the natural evolution of antibiotics and may reveal an evolution-based approach to discovering novel antibiotics.  Congratulations, Bach!

In this work, Hai found that DarE radical SAM enzyme uses O2 to form the ether crosslink in the darobactin A biosynthesis. This is the first radical SAM enzyme that uses O2 as a co-substrate. In general, radical SAM enzymes are known to be inactivated by O2. Thus, this finding significantly extends the scope of radical SAM catalysis.

As a conclusion of the summer undergraduate research fellowship in Chemistry (SURF), Elisha and Rachel presented their work in the SURF conference.  They were both very busy explaining their achievements to the audience.  Very well done!  Also kudos to their mentors, Abhi and Hai.  We all feel very proud of both of you for your development over the summer and the past year.  Hope to see your study flourish even more in the Fall and beyond.  

Our paper on the chitin synthase (CHS) structure in collaboration with the Lee lab at Duke was published online on Nature Structural & Molecular Biology.  This paper reports the first 3D structure of CHS2 from Candida albicans in complex with substrate or inhibitors including nikkomycin Z.  CHS is a proven target of antifungals that are currently used for agricultural purposes or under clinical investigation. This work is an important step toward our atomic resolution understanding of catalysis, inhibition, and regulation of CHS and is critical for the future structure-guided development of CHS-targeting antifungals.

Haoran successfully defended his Ph.D. dissertation on April 1.  He received many compliments for his achievements represented by a comment by Prof. Oas saying that among the theses he had seen, Haoran’s thesis had the most diverse biophysical methods applied to solve the important biochemical question.  Haoran will move on to a postdoc position in Wenjun Zhang’s lab at UC Berkeley.  Congratulations, Haoran, and wish you continue your strong career!