Holly Ellis

Associate Professor

Wake Forest University, Ph.D., 1998

Texas A&M University, Postdoctoral Associate, 2001

ellishr@auburn.edu

Our research interests are in the area of mechanistic enzymology with a particular focus on oxygenases involved in sulfur metabolism. We have focused on a bacterial two-component system involved in sulfur acquisition, and a mammalian metabolic pathway important in taurine biosynthesis.

Alkanesulfonate Monooxygenase System

          For many bacterial organisms, inorganic sulfate is an important metabolite in the biological synthesis of sulfur-containing macromolecules. Inorganic sulfur is poorly represented in aerobic soil therefore bacteria in soil environments must have alternative sources for obtaining this element. When Escherichia coli is deprived of inorganic sulfur or cysteine a set of sulfate-starvation-induced (Ssi) proteins is produced at increased levels. Two of these proteins include an FMN reductase (SsuE) and an FMNH2-utilizing monooxygenase (SsuD). This two-component enzyme system is involved in the acquisition of sulfur through the reduction of alkanesulfonates to sulfites and the corresponding aldehyde. The alkanesulfonate monooxygenase system belongs to a family of two-component enzyme systems that utilize FMN as a substrate rather than a bound prosthetic group. The number of bacterial flavin-dependent monooxygenases that utilize flavin as a substrate has increased significantly with new systems continually being identified. Despite the growing number and metabolic importance of these two-component systems, the mechanism of flavin transfer has not been fully determined. We are interested in characterizing the desulfonation reaction, and how the mechanism of flavin transfer is related to other bacterial two-component flavin systems that utilize flavin as a substrate.

Taurine Biosynthetic Pathway

           The sulfur-containing nonprotein amino acid, taurine, plays an important protective role in a wide variety of mammalian physiological functions. Many of the biological functions of taurine rely on the intracellular concentrations of taurine, which is determined by the cells capacity to synthesize this metabolite. Taurine can be synthesized by several different mechanisms, but is primarily produced by the cysteine dioxygenase pathway. In the initial reaction, cysteine is converted to cysteine sulfinic acid by the enzyme cysteine dioxygenase. The reaction catalyzed by cysteine dioxygenase (CDO) has been shown to be a primary step in the production of taurine. The cysteine sulfinic acid formed can branch to form pyruvate and sulfite by aspartate amino transferase or taurine by cysteine sulfinate decarboxylase (CSD). By catalyzing the first step in the pathway, CDO plays a critical role in the maintenance of cysteine/taurine levels in cells. The focus of our research is to obtain a detailed understanding of the catalytic mechanism of each enzyme in the taurine biosynthetic pathway.

References:

Abdurachim, K.; Ellis, H. R. Detection of Protein-Protein Interactions in the Alkanesulfonate Monooxygenase System from Escherichia coli. Submitted to Journal of Bacteriol. 2006, in press.

Gao, B.; Ellis, H. R. Altered mechanism of the alkanesulfonate FMN reductase with the monooxygenase enzyme. Biochem and Biophys Res Commun. 2005, 331, 1137-1145. 

Gao, B.; Bertrand, A.; Boles, W. H.; Ellis, H. R.; Mallett, T. C. Crystallization and preliminary x-ray crystallographic studies of the alkanesulfonate FMN reductase from Escherichia coli. Acta Crystallographica, Section F: Structural Biology and Crystallization Communications. 2005 F61, 837-840.