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A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

Andersen, Gorm LU ; Andersen, Birgit LU ; Dobritzsch, Doreen; Schnackerz, Klaus D. and Piskur, Jure LU (2007) In The FEBS Journal 274(7). p.1804-1817
Abstract
In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal... (More)
In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V-max/K-m = 0.78 U.mg(-1).mM(-1)), but can also use GABA (V-max/K-m = 0.42 U.mg(-1).mM(-1)), while SkUga1p only uses GABA (V-max/K-m = 4.01 U.mg(-1).mM(-1)). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
gene duplication, gamma-aminobutyrate, aminotransferase, beta-alanine, Saccharomyces kluyveri
in
The FEBS Journal
volume
274
issue
7
pages
1804 - 1817
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000244883400017
  • scopus:33947244361
ISSN
1742-464X
DOI
10.1111/j.1742-4658.2007.05729.x
language
English
LU publication?
yes
id
0be02a97-07f7-490c-94c9-a7abb77a7502 (old id 670462)
date added to LUP
2007-12-05 10:17:04
date last changed
2017-01-01 07:21:58
@article{0be02a97-07f7-490c-94c9-a7abb77a7502,
  abstract     = {In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V-max/K-m = 0.78 U.mg(-1).mM(-1)), but can also use GABA (V-max/K-m = 0.42 U.mg(-1).mM(-1)), while SkUga1p only uses GABA (V-max/K-m = 4.01 U.mg(-1).mM(-1)). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity.},
  author       = {Andersen, Gorm and Andersen, Birgit and Dobritzsch, Doreen and Schnackerz, Klaus D. and Piskur, Jure},
  issn         = {1742-464X},
  keyword      = {gene duplication,gamma-aminobutyrate,aminotransferase,beta-alanine,Saccharomyces kluyveri},
  language     = {eng},
  number       = {7},
  pages        = {1804--1817},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {The FEBS Journal},
  title        = {A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast},
  url          = {http://dx.doi.org/10.1111/j.1742-4658.2007.05729.x},
  volume       = {274},
  year         = {2007},
}