Dr Ken Yokoyama, Ph.D.

February 4, 2017October 25, 2017

Welcome Hai!

Dr. Hai P. Nguyen joined us to study fungal cell wall biosynthesis. He received a Ph.D. degree from University of Toledo. One of his key achievements was a successful development of a synthetic method to construct beta-mannosides, one of the most challenging glycosidic linkages to create using synthetic approaches. In our lab, Hai will work on development of chemical biology approaches to study fungal cell wall biosynthesis and the mechanism of action of antifungals. He will also work partially on the molybdenum cofactor biosynthesis.

September 21, 2016November 21, 2016

Our work on nikkomycin and polyoxin biosynthesis was published in Nature Chemical Biology

Our recent discovery of novel radical SAM enzyme that catalyzes free-radical mediated C-C bond formation during nikkomycin and polyoxin biosynthesis was published online in Nature Chemical Biology. The work is highlighted on the journal’s top page. Our studies showed that biosynthetic routes to nikkomycins and polyoxins proceeds via a bicyclic intermediate, octosyl acid phosphate (OAP), formed by a free radical mediated ring closure catalyzed by the radical SAM enzyme, PolH. We also propose OAP to be a common biosynthetic intermediate for various antifungal nucleosides, and PolH as the genetic marker for genome mining discovery of these natural products. Edward A. Lilla, a graduate student, performed all the characterizations described in the paper.

divergent-biosynthesis

August 8, 2016October 25, 2017

Pneumocandin paper was published in ACS Chemical Biology

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.

August 3, 2016August 3, 2016

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!!

HS picture

May 22, 2016

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.

April 10, 2016April 11, 2016

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.

April 10, 2016April 12, 2016

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.

April 9, 2016April 10, 2016

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.

February 1, 2016April 10, 2016

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)

December 1, 2015November 21, 2016

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.