Date of Award

5-2010

Degree Type

Report

Degree Name

Master of Science (MS)

Department

Chemistry and Biochemistry

First Advisor

Scott Ensign

Abstract

A number of bacteria are capable of growth with acetone and acetophenone as their sole sources of carbon and/or energy. The pathways and enzymes involved in the transformation of these molecules into useable carbon and energy are unique. Among these are two novel enzymes, acetone carboxylase and acetophenone carboxylase, which represent a fundamentally novel classes of carboxylases.

The initial step in acetone metabolism, in X. autotrophicus st Py2, R. capsulatus st B10 and R. rhodochrous, is the thermodynamically unfavorable reaction to yield acetoacetate. This step is catalyzed by the enzyme acetone carboxylase and is coupled with the unprecedented, concomitant hydrolysis of two phosphoanhydride bonds of ATP. This enzyme also requires two tightly bound Mn2+ ions, among other co-factors, for catalytic activity.

In a similar, albeit distinct manner, acetophenone carboxylase catalyzes the carboxylation of acetophenone to benzoylacetate. Reminiscent of acetone carboxylase, carboxylation activity in this enzyme is dependent on the hydrolysis of ATP to ADP and inorganic phosphate. Catalytic activity is also dependent on Zn2+ and either of Mn2+ or Mg2+ as co-factors. Additionally, similar to acetone carboxylase, acetophenone carboxylase shows uncoupled ATPase activity with either bicarbonate or acetophenone in the absence of a second substrate. This indicates that both substrates may be phosphorylated.

The studies on acetone and acetophenone carboxylase have expanded our knowledge on the novel mechanisms and cofactors involved in the metabolism of toxic, reactive, xenobiotic molecules such as acetone and acetophenone. Further, as in the case of acetone carboxylase, homologs of these enzymes are found in higher organisms such as mammals. The biochemical and mechanistic properties of these enzymes may be relevant to the modes of action of these homologs. In this report, using the work currently accomplished on these enzymes, and by discussing their salient features, an effort has been made to provide a detailed insight into these enzymes.

Share

COinS