Chemical and chemoenzymatic syntheses of bacillithiol: a unique low-molecular-weight thiol amongst low G + C Gram-positive bacteria

Sharma, Sunil V., Jothivasan, Vishnu K., Newton, Gerald L., Upton, Heather, Wakabayashi, Judy I., Kane, Melissa G., Roberts, Alexandra A., Rawat, Mamta, La Clair, James J., and Hamilton, Chris J. (2011) Chemical and chemoenzymatic syntheses of bacillithiol: a unique low-molecular-weight thiol amongst low G + C Gram-positive bacteria. Angewandte Chemie International Edition, 50 (31). pp. 7101-7104.

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Abstract

In eukaryotes and Gram-negative bacteria, the cysteinyl tripeptide glutathione (GSH, Figure 1) is the predominant low-molecular-weight thiol. It plays a critical role in maintaining an intracellular reducing environment and serves many other important metabolic functions.⁽¹⁾ For instance, the reversible formation of GS-S-protein disulfides (glutathionylation) is an important post-translational modification for regulating protein function and protecting exposed cysteine residues from irreversible oxidative damage.⁽²⁾ Glutathione-Stransferases also mediate xenobiotic detoxification by S conjugation with GSH. Most Gram-positive bacteria lack GSH, but instead produce other, distinctly different low-molecular weight thiols. Gram-positive high G+C content actinobacteria produce mycothiol (MSH, Figure 1), which serves analogous functions to GSH.⁽³⁾ Low G+C Gram-positive bacteria (Firmicutes) produce neither GSH nor MSH and until recently the identity of their major, cysteine-derived, low-molecular-weight thiol has been elusive. In 2007, an unknown 398 Da thiol was observed in Bacillus anthracis cell extracts⁽⁴⁾ and in Bacillus subtilis as a mixed disulfide with the redox controlled ohr regulator protein (OhrR).⁽⁵⁾ The same thiol was subsequently isolated by treating Deinococcus radiodurans cell extracts with monobromobimane (mBBr) from which the structure of bacillithiol (BSH, 1) was then elucidated as its corresponding fluorescently labeled Sbimane (mB) derivative BSmB (3, Figure 1).⁽⁶⁾

Item ID: 25726
Item Type: Article (Research - C1)
ISSN: 1521-3773
Keywords: Firmicutes; fosfomycin; natural products; thiol-s-transferase; total synthesis
Date Deposited: 15 May 2013 02:14
FoR Codes: 03 CHEMICAL SCIENCES > 0305 Organic Chemistry > 030503 Organic Chemical Synthesis @ 70%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060107 Enzymes @ 10%
03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules @ 20%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 80%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 20%
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