Our latest publication about pneumocandin biosynthesis in collaboration with Dr. Gerald Bills at the University of Texas was accepted to ACS Chemical Biology. This work revealed the mechanism of product release from lipid synthesizing PKS, and its application to create pneumocandin analogs. Anna performed 1,3-glucan synthase inhibition assays of the structurally novel pneumocandin analogs.
Welcome, Hilda
Dr. Hilda Sucipto joined the lab as a postdoc fellow. Hilda graduated from the Rolf Müller lab with an outstanding achievements in understanding the biosynthesis of myxopyronin, an antibacterial antibiotics with novel mode of action. In our lab, Hilda will work on antifungal antibiotics biosynthesis and their engineering. Welcome and let’s enjoy exciting science together!!
Sojourn in Biochemistry Conference: Stubbe Symposium
A conference to celebrate JoAnne Stubbe’s 70th birthday will be held in Boston MA on June 11-12. Most of the Stubbe lab alumni and many collaborators (~130 attendees) will gather and discuss their latest progress. Ken will give a talk and Edward will present a poster. Thank you Marty (Bollinger) and Dan (Nocera) for organizing such an exciting event. Looking forward to see friends and new people.
Our new web site is now launched!!
We are interested in the functions and mechanisms of enzymes involved in the biosynthesis of natural products and cofactors as well as those in fungal cell wall biosynthesis. The target enzymes play essential roles in inheritable human disease, or bacterial or fungal infectious disease. We aim to understand the mechanisms of these enzymes and use the knowledge to discover novel therapeutics. Specifically, we are interested in:
(1) Cofactor biosynthesis in humans and pathogenic bacteria.
(2) Antifungal biosynthesis and genome mining.
(3) Fungal cell wall biosynthesis and antifungal mode of action.
We use a combination of approaches from organic chemistry, biochemistry, molecular biology and spectroscopy with particular focus on in vitro functional and mechanistic characterization of enzymes, small molecule characterization, bacterial and fungal/yeast genetics, synthetic organic chemistry, NMR, EPR and fluorescence microscopy.
Ken gave an invited talk in the ASBMB annual meeting
This year’s ASBMB annual meeting was held in San Diego between April 2 – 6. Ken was invited to give a talk about our recent progress in the Moco project. He also chaired a session for structure studies of complex systems in Bioinorganic Catalysis. The program is available online.
Our MoaC paper (PNAS 2015) was featured as an article “of outstanding importance”
In the recent review article in the Current Opinion in Chemical Biology by Guenter Schwarz, our MoaC structure paper (PNAS 2015) was referenced and highlighted as an article of outstanding interest. This review paper nicely summarizes the current status of the research in Moco biosynthesis and human Moco deficiency disease. The author referenced four of our original research publication with the PNAS 2015 paper as the work that settled the discussion about the functions of MoaA and MoaC.
Abhi received a poster award in the Biochemistry Department 2016 annual retreat
Each year, ~4 students receive poster awards during our department retreat. This year, Abhi received a poster award, joining our previous recipients; Edward (2014 retreat) and Brad (2011 and 2013 retreat). So far, we have a record of four-straight years!! (note: we did not have retreat in 2012)
Our work on the MoaC mechanism was published in ACS Biochemistry
This paper describes successful entrapment of previously uncharacterized reaction intermediate of MoaC reaction using an uncleavable substrate analog, 3′,8-cH2GTP. Intriguingly, the trapped intermediate was tightly bound to MoaC, likely through covalent modification, making the analog as the first mechanism-based inhibitor of bacterial Moco biosynthesis. The results revealed that the unique tetracyclic structure of cPMP (MoaC product) was constructed via a concerted formation of pterin and cyclic phosphate rings, which is distinct from previously proposed stepwise mechanism. Brad found the irreversible inhibition and performed most of the basic characterization, and Edward performed some nice follow up experiments including the MS characterization of the inhibited MoaC.