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Acetylation of homoserine is required for methionine biosynthesis in Streptococcus pneumoniae
Author(s) -
Nguyen Minh,
Born Timothy L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1016-d
Subject(s) - homoserine , biochemistry , biosynthesis , succinylation , methionine , isoleucine , serine , threonine , chemistry , acetylation , enzyme , amino acid synthesis , lysine , amino acid , stereochemistry , quorum sensing , gene , leucine , virulence
The metabolite homoserine occupies an important juncture between methionine, lysine, threonine, and isoleucine biosynthesis, and its fate is tightly controlled. Flux of homoserine into the methionine biosynthetic pathway is controlled at the first unique step, acylation of the gamma hydroxyl of homoserine. Two separate acylations have been identified in microorganisms: acetylation, using acetyl‐CoA as the acyl donor and succinylation, using succinyl‐CoA as the acyl donor. The enzymes catalyzing these two acyl transfers have no amino acid sequence similarity and appear to have evolved independently. The transsuccinylase gene from the clinically relevant pathogen Streptococcus pneumoniae was PCR‐amplified and expressed in E. coli . Characterization of this enzyme demonstrated that it uses acetyl‐CoA as its preferred substrate, rather than succinyl‐CoA. This is the second documented instance of a putative succinyltransferase utilizing acetyl‐CoA. A kinetic characterization of the enzyme is presented, including substrate specificity profiles, pH dependence curves, and analysis of site‐specific mutants. The results of this study are relevant for the design of novel antibacterial compounds.