Molecular evolution of acetohydroxyacid synthase in bacteria

Abstract

Acetohydroxyacid synthase (AHAS) is the key enzyme in the biosynthetic pathways of branched chain amino acids in bacteria. Since it does not exist in animal and plant cells, AHAS is an attractive target for developing antimicrobials and herbicides. In some bacteria, there is a single copy of AHAS, while in others there are multiple copies. Therefore, it is necessary to investigate the origin and evolutionary pathway of various AHASs in bacteria. In this study, all the available protein sequences of AHAS in bacteria were investigated, and an evolutionary model of AHAS in bacteria is proposed, according to gene structure, organization and phylogeny. Multiple copies of AHAS in some bacteria might be evolved from the single copy of AHAS, the ancestor. Gene duplication, domain deletion and horizontal gene transfer might occur during the evolution of this enzyme. The results show the biological significance of AHAS, help to understand the functions of various AHASs in bacteria, and would be useful for developing industrial production strains of branched chain amino acids or novel antimicrobials.

Cloning, Expression, Enzymatic Characterization and Mechanistic Studies of M13 Mutant Acetohydroxyacid Synthase That Rescues Valine Feedback Inhibition

“…It consists of large and small subunits that form a multimeric group, with the large subunit performing its catalytic function and containing the binding sites of thiamine diphosphate, flavin adenine dinucleotide, and magnesium (Mg 2+ ) [2,3] and the small subunit acting as a regulator, containing binding sites for branched-chain amino acids and enhancing catalytic subunit (CSU) activity [4,5]. The CSUs of prokaryotes and eukaryotes have relatively conserved amino acid sequences and peptide lengths, which results in their identical sizes (approximately 60 kDa) [6,7]. The regulatory subunits (RSUs) of AHAS vary in size, with the RSU of AHAS reaching 55 kDa [4] in eukaryotes and ranging from 9 to 17 kDa [7] in prokaryotes.…”

“…The CSUs of prokaryotes and eukaryotes have relatively conserved amino acid sequences and peptide lengths, which results in their identical sizes (approximately 60 kDa) [6,7]. The regulatory subunits (RSUs) of AHAS vary in size, with the RSU of AHAS reaching 55 kDa [4] in eukaryotes and ranging from 9 to 17 kDa [7] in prokaryotes.…”