The Chemistry of Life Processes Program in the Chemistry Division funds this award. Professor Michael Toney of the University of California-Davis investigates vitamin B6 dependent enzymes. Enzymes catalyze the chemical reactions of living systems, enhancing the rates of reaction by enormous amounts. A large class of metabolically-important enzymes use vitamin B6 (pyridoxal phosphate) to catalyze reactions for nitrogen utilization. As a class, these enzymes also have excellent potential for the synthesis and commercial production of high-value chemicals (such as herbicides). The goal of this research is to understand the basis for the specific production of certain chemicals by vitamin B6 dependent enzymes. To achieve this goal, a combination of studies on altered versions of vitamin B6, and laboratory enzyme evolution is underway. This funding contributes to the professional development of undergraduate and graduate students, and allows the development of an undergraduate course focused on preparing under-represented minority undergraduate students for laboratory research.
Pyridoxal phosphate (also called PLP or vitamin B6) dependent enzymes are central to nitrogen metabolism in all organisms. As a group, they catalyze more than a dozen different reaction types, with each reaction type having multiple substrate specificities. Approximately 230 different PLP enzyme activities have been identified to date. The fundamental organic chemistry used to catalyze these different reactions is generally understood, but the mechanisms by which substrate and reaction specificity are achieved are not. This research has two major components: the first employs coenzyme analogues to determine the influence of coenzyme electrophilicity on reaction specificity, and the second involves laboratory reconstruction of ancestral, non-specific enzymes and recapitulation of their evolution to present day enzymes via a minimal number of critical mutations. These studies help to define the electronic and structural determinants of reaction specificity in pyridoxal phosphate dependent enzymes. This funding also contributes to professional development of undergraduate and graduate students, and allows for the development of an undergraduate course focused on preparing under-represented minority undergraduate students for laboratory research.
