91³Ô¹ÏÍø

Neupane, T., Chambers, L. R.*, Godfrey, A. J.*, Monlux, M. M.*, Jacobs, E. J.*, Whitworth, S.*, Spawn, J. E.*, Clingman, S. H. K.*, Vergunst, K. L., Niven, F. M., Townley, J. J.*, Orion, I. W.*, Goodspeed, C. R.*, Cooper, K. A.*, Cronk, J. D., Shepherd, J. N. and Langelaan D. L. (2022) Microbial rhodoquinone biosynthesis proceeds via an atypical RquA-catalyzed amino transfer from S-adenosyl-L-methionine to ubiquinone, Commun. Chem., 5, 89.

Salinas, G., Langelaan, D. N. and Shepherd, J. N. (2020) Rhodoquinone in bacteria and animals: Two distinct pathways for biosynthesis of this key electron transporter used in anaerobic bioenergetics. Biochim. Biophys. Acta Bioenergetics, 1861, 148278.  

Tan, J. H., Lautens, M., Romanelli-Cedrez, L., Wang, J., Schertzberg, M. R., Reinl, S. R.*, Davis, R. E., Shepherd, J. N., Fraser, A. G., Salinas, G. (2020) Alternative splicing of coq-2 controls of the level of rhodoquinone in animals. eLife, 9, e56376. 

Roberts Buceta, P. M.*, Romanelli-Cedrez, L., Babcock, S. J.*, Xun, H.*, VonPaige, M. L.*, Higley, T. W.*, Schlatter, T. D.*, Davis, D. C.*, Drexelius, J. A.*, Culver, J. C.*, Inés Carrera, I., Shepherd, J. N. and Salinas, G. (2019) The kynurenine pathway is essential for rhodoquinone biosynthesis in Caenorhabditis elegans. J. Biol. Chem., 294, 11047-11053.  
Bernert, A. C., Jacobs, E. J.*, Reinl, S. R.*, Choi, C. C. Y.*, Roberts Buceta, P. M.*, Culver, J. C.*, Goodspeed, C. R.*, Bradley, M. C., Clarke, C. F., Basset, G. J. and Shepherd, J. N. (2019) Recombinant RquA catalyzes the in vivo conversion of ubiquinone to rhodoquinone in Escherichia coli and Saccharomyces cerevisiae, BBA Mol. Cell Biol. Lipids, 1864, 1226-1234. 

Campbell, A. R. M.*, Titus, B. R.*, Kuenzi, M. R.*, Rodriguez-Perez, F.*, Brunsch, A. D. L.*, Schroll, M. M.*, Owen, M. C.*, Cronk, J. C., Anders, K. R. and Shepherd, J. N. (2019) Investigation of candidate genes involved in the rhodoquinone biosynthetic pathway in Rhodospirillum rubrum, PLoS ONE, 14, e0217281.

Stairs, C. E., Eme, L., Muñoz-GÏŒmez, S. A., Cohen, A., Dellaire, G., Shepherd, J. N., Fawcett, J. P. and Roger, A. W. (2018) Microbial eukaryotes have adapted to hypoxia by horizontal acquisitions of a gene involved in rhodoquinone biosynthesis, eLife, 7, e34292.

Lonjers, Z. T.*, Dickson, E. L.*, Chu, T-P T.*, Kreutz, J. E.*, Neacsu, F. A., Anders, K. R. and Shepherd, J. N. (2012) Identification of a new gene required for the biosynthesis of rhodoquinone in Rhodospirillum rubrum, J. Bacteriol., 194, 965-971.

Brajcich, B. C.*, Iarocci, A. L.*, Johnstone, L. A. G.*, Morgan, R. K.*, Lonjers, Z. T.*, Hotchko, M. J.*, Muhs, J. D.*, Kieffer, A.*, Reynolds, B. J., Mandel, S. M., Marbois, B. N., Clarke, C. F. and Shepherd, J. N. (2010) Evidence that ubiquinone is a required intermediate for rhodoquinone biosynthesis in Rhodospirillum rubrum, J. Bacteriol., 192, 436-445.

(* indicates 91³Ô¹ÏÍø student author)

The broader impacts of Dr. Shepherd’s research involve the development of new treatments for parasitic infections, which are neglected tropical diseases that affect more than 1.5 billion people worldwide (WHO 2019). In order to combat this disease, Dr. Shepherd’s research team has sought to elucidate the biosynthetic pathway of rhodoquinone (RQ) as a unique target for the design of new anti-parasitic drugs. RQ is an essential electron carrier used in the anaerobic energy metabolism of species such as the parasitic helminths, the free-living nematode Caenorhabditis elegans (C. elegans), and the purple non-sulfur bacterium, Rhodospirillum rubrum (R. rubrum). RQ is not synthesized or used in humans and other mammalian hosts with a primarily aerobic energy metabolism. Dr. Shepherd’s group discovered a signature gene required for RQ biosynthesis in R. rubrum called rquA, and recently they have made important advances in RQ biosynthesis in C. elegans, which is an excellent model for the helminth parasites.

Research Grants Funded

“Rhodoquinone biosynthesis as an unorthodox treatment for microbial infection and oxygen deprivation,” New Frontiers in Research Fund – Exploration, $300,000, for award period: 4/1/19 – 3/31/23 ($80,000 for 91³Ô¹ÏÍø University). Role: Co-investigator with PI David Langelaan from Dalhousie University, NS

“Elucidation and Regulation of Rhodoquinone Biosynthesis in Rhodospirillum rubrum,” National Institutes of Health, AREA R-15 program, $241,355, for award period: 8/1/11-7/31/15. Role: PI

“RUI: Purchase of a Liquid Chromatograph Time-of-Flight Mass Spectrometer,” National Science Foundation, CRIF-MU program, $286,753, for award period: 2/1/08-1/31/11. Role: PI with Co-PI’s Joanne Smieja, Stephen Warren, Jeff Watson and Jeff Cronk.

“CAREER: Rhodoquinone Biosynthesis and Anthelmintic Agent Design,” National Science Foundation, Division of Chemistry, $355,000 for award period: 9/01/02 – 8/31/07. Role: PI

“RUI: Acquisition of a 300 MHz Nuclear Magnetic Resonance Spectrometer,” National Science Foundation, Division of Chemistry Instrumentation and Facilities, $133,795 for award period: 9/01/00 - 8/31/03. Role: PI with Co-PI’s David Cleary, Joanne Smieja and Kay Nakamaye.

“The Biosynthesis of Rhodoquinone: A New Target for Anthelmintic Drug Design,” Research Corporation, Cottrell College Science Award, $42,738 for award period: 06/01/00 - 09/01/01. Role: PI

Recent Presentations with 91³Ô¹ÏÍø Undergraduates 

1. Jennifer N. Shepherd, Lydia R. Chambers*, Trilok Neupane and David Langelaan, “Rhodoquinone biosynthesis in microbes is catalyzed by RquA via an unusual manganese-dependent amino transfer from S-adenosyl-L-methionine to ubiquinone,” invited speaker for the Cofactor Biosynthesis session at the 21st European Bioenergetics Conference, Aix-en-Provence, France, August 20-25, 2022. 
2. 2021 Experimental Biology Conference (ASBMB Annual Meeting), April 27-30, 2021.
   (a) Lydia Rose Chambers*, Alexander Godfrey*, Melina Monlux*, Trilok Neupane, David L. Langelaan, and Jennifer N. Shepherd, “Determination of Factors Required for RquA Function via an in Vitro Assay,” virtual poster presentation.
   (b) Sophia Whitworth*, Jamie Spawn*, Christina Choi*, Samantha Reinl*, Laura Diaz-Martinez and Jennifer N. Shepherd, “Further Investigation of the Biosynthesis and Function of Rhodoquinone,” virtual poster presentation.
3. 2017 Experimental Biology Conference (ASBMB Annual Meeting), Chicago, IL, April 22-25, 2017:
   (a) Shannon Babcock* and Jennifer N. Shepherd, “Elucidating the Biosynthetic Pathway of Rhodoquinone in C. elegans,” poster presentation.
   (b) Amanda Martin* and Jennifer N. Shepherd, “Determining the Rhodoquinone Biosynthetic Pathway in Rhodospirillum rubrum Using Gene Knock-outs, “poster presentation.
   (c) Alison Zander* and Jennifer N. Shepherd, “Overexpression and Characterization of the rquA Gene Product Involved in the Biosynthesis of Rhodoquinone,” poster presentation.
4. 249th American Chemical Society National Meeting, Denver, CO, March 26-28, 2015:
   (a) Madeline Kuenzi* and Jennifer N. Shepherd, “Effects of deletion of the Rru_A3004 gene on rhodoquinone biosynthesis in Rhodospirillum rubrum,” poster presentation.
   (b) Benjamin Titus* and Jennifer N. Shepherd, "Analysis of rhodoquinone production in knockout strain candidates in Rhodospirillum rubrum," poster presentation.
   (c) Helen Xun* and Jennifer N. Shepherd, “Identification of Genes Involved in RQ9 Biosynthesis in C. elegans using RNAi Knockdowns,” poster presentation.
5. 247th American Chemical Society National Meeting, Dallas, TX, March 17, 2014:
   (a) Adam Blount* and Jennifer N. Shepherd, “The purification and characterization of RquA,” poster presentation.
   (b) Alysha Labrum* and Jennifer N. Shepherd, “Investigation of putative GATase genes for the rhodoquinone biosynthesis pathway of R. rubrum via gene knockouts,” poster presentation.
6. Monica Schroll* and Jennifer N. Shepherd, “Identification of an amidotransferase gene required for rhodoquinone biosynthesis in Rhodospirillum rubrum,” poster presentation at the American Society for Microbiology Meeting, Denver, CO, May 18, 2013.
7. Erin L. Dickson* and Jennifer N. Shepherd, "Characterization of a Putative Methyltransferase Involved in Rhodoquinone Biosynthesis in Rhodospirillum rubrum," poster presentation at the American Chemical Society 243rd National Meeting, San Diego, CA, March 26, 2012.