Abstract

In this paper, we demonstrate that a protein from Bacillus subtilis (YqjM) shares many characteristic biochemical properties with the homologous yeast Old Yellow Enzyme (OYE); the enzyme binds FMN tightly but noncovalently, preferentially uses NADPH as a source of reducing equivalents, and forms charge transfer complexes with phenolic compounds such as p-hydroxybenzaldehyde. Like yeast OYE and other members of the family, YqjM catalyzes the reduction of the double bond of an array of alpha,beta-unsaturated aldehydes and ketones including nitroester and nitroaromatic compounds. Although yeast OYE was the first member of this family to be discovered in 1933 and was the first flavoenzyme ever to be isolated, the physiological role of the family still remains obscure. The finding that alpha,beta-unsaturated compounds are substrates provoked speculation that the OYE family might be involved in reductive degradation of xenobiotics or lipid peroxidation products. Here, for the first time, we demonstrate on the protein level that whereas YqjM shows a basal level of expression in B. subtilis, the addition of the toxic xenobiotic, trinitrotoluene, leads to a rapid induction of the protein in vivo denoting a role in detoxification. Moreover, we show that YqjM is rapidly induced in response to oxidative stress as exerted by hydrogen peroxide, demonstrating a potential physiological role for this enigmatic class of proteins.

Highlights

  • Old Yellow Enzyme (EC 1.6.99.1), originally isolated from brewers’ bottom yeast, was the first enzyme shown to contain a bound flavin (FMN) [1, 2], a cofactor typically found to participate in biological redox reactions

  • We demonstrate that a protein from Bacillus subtilis (Yq jM) shares many characteristic biochemical properties with the homologous yeast Old Yellow Enzyme (OYE); the enzyme binds FMN tightly but noncovalently, preferentially uses NADPH as a source of reducing equivalents, and forms charge transfer complexes with phenolic compounds such as p-hydroxybenzaldehyde

  • The biochemical properties of B. subtilis Yq jM presented confirm that this protein belongs to the family of flavoprotein oxidoreductases exemplified by yeast OYE

Read more

Summary

EXPERIMENTAL PROCEDURES

Molecular Techniques—Basic molecular techniques were adopted from Ausubel et al [16] or Sambrook et al [17]. The open reading frame of B. subtilis yq jM was amplified by the polymerase chain reaction (PerkinElmer Life Sciences), using the isolated genomic DNA as template while incorporating appropriate restriction sites, and cloned into the NdeI and XhoI restriction sites of pET21a (Novagen) This allows expression of authentic B. subtilis Yq jM under control of the isopropyl-1-thio-␤-Dgalactopyranoside-inducible T7 promoter. The assays were performed in the presence of an oxygenconsuming system (20 mM glucose, 10 units of glucose oxidase) at 25 °C in 1 ml of 100 mM Tris buffer, pH 7.5, containing either 100 ␮M ␤-NADPH or 100 ␮M ␤-NADH, and by adding Yq jM at concentrations ranging from 3.89 to 19.4 nM depending on the reaction rate being observed with the particular substrate. The software Sigma Plot version 4.14 (Jandel Scientific) was used for the evaluation of the data

RESULTS
Ligand pKaa
Substrate kcat
DISCUSSION
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call