Escalante Lab

About our Lab

Overview

I am interested in bacterial and archaeal metabolism and physiology. My research group is currently focused on three areas.

Complex metabolic pathway analysis

Figure 2For over two decades, we have investigated multiple aspects of the biosynthesis of adenosylcobalamin (AdoCbl, coenzyme B12) in bacteria and archaea. We have discovered new enzymes and pathways in archaea and bacteria for the assimilation of incomplete corrinoids and other precursors from the environment.

We recently discovered a strategy for the synthesis of specific structural variants of the coenzyme that may allow organisms to outcompete others in their environment. It is remarkable that even though the biosynthesis of coenzyme B12 has been studied for decades, we still have an incomplete picture of how the assembly of this complex molecule is achieved, and have almost no information of why this major biosynthetic pathway is intimately associated with the cell membrane in all organisms known to make it. We have made numerous contributions to our understanding of the biochemistry and genetics of AdoCbl biosynthesis, but the goal is to provide a physiological framework for this major biosynthetic pathway.

Sirtuins and metabolic pathway integration

Acylation of the epsilon amino group of the side chain of lysine is a post-translational modification that has been extensively studied in eukaryotes, but only to a limited extent in bacteria and archaea. Our goal is to understand the physiological roles of lysine acylation in prokaryotic systems. Bioinformatics analyses suggest that prokaryotic modifying/de-modifying systems are diverse, and in some microorganisms the number or putative modifying enzymes is large.

Fundamental information about these systems is lacking. For example, the substrates for most of these putative enzymes are not known. In fact, we do not know whether the substrates are small molecules, nucleic acids, proteins, etc. The effects of the absence or overproduction of these systems is also unclear. Our lab has made seminal contributions to the field, and is actively pursuing several projects in this area of research.

Metabolic stress caused by toxic metabolites

This area of our work centers on the catabolism of acetate and propionate, two short-chain fatty acids that are abundant in soil and the gut, but whose catabolism generates potent inhibitors. Our work in this area stems from our discovery of the genes encoding the enzymes needed to catabolize propionate, and the assignment of their biochemical activities. Our work led to the discovery of the 2-methylcitric acid cycle as the predominant pathway of propionate catabolism in bacteria.

 

Figure 3

 

Currently, we are investigating the molecular basis of acetate and propionate toxicity, and the mechanisms used by the cell to avoid the toxic effects of these compounds. Recently, we showed that cells that cannot catabolize 2-methylcitrate are glucose auxotrophs, and that such auxotrophy is due to inhibitory effects of 2-methylcitrate on fructose biphosphatase, a key gluconeogenic enzyme. Our goals is to continue to identify other functions affected by 2-methylcitrate.

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Location
527 Biological Sciences Building
120 Cedar Street
Athens, GA 30602

Contact Info
Phone: 706-542-2651
E-mail: jcescala@uga.edu