Bacillithiol (BSH or Cys-GlcN-mal) is a
thiol compound found in Bacillus species.[1] It is likely involved in maintaining cellular redox balance and plays a role in microbial resistance to the antibiotic
fosfomycin.
Structure
Chemically, it is a glycoside formed between L-cysteinyl-D-glucosamine and
malic acid. It was isolated and identified (as its bacillithiol-S-
bimane derivative) in 2009 from Staphylococcus aureus and Deinococcus radiodurans,[1] although it was first detected in 2007, as an unidentified thiol in Bacillus anthracis.[2] The naturally occurring free thiol form of bacillithiol has since been synthesised and characterised along with its biosynthetic precursors and its symmetrical disulfide.[3]
Biological role
Bacillithiol appears to participate in the sensing of
peroxides by Bacillus,[4] but may also substitute for
glutathione, which is the most common intracellular
thiol in eukaryotes and some bacteria.[1] Some of the genes involved in the biosynthesis of bacillithiol were identified and characterised in 2010.[5] Bacteria engineered to be deficient in bacillithiol demonstrated increased sensitivity to various electrophilic
xenobiotic compounds, including the antibiotic
fosfomycin, suggesting that in these organisms the mechanism of
fosfomycin resistance relies on the presence of bacillithiol.[5] Furthermore, in vitro kinetic studies have established that bacillithiol is a preferred thiol substrate for the antibiotic resistance enzyme FosB.[3][6]
Biosynthesis
Bacillithiol is produced via the enzymes BshA, BshB, and BshC. BshA replaces the
UDP group on
UDP-N-acetylglucosamine with an
L-malyl group. BshB then removes the
acetyl group. L-Cysteine is added to the resulting free amine, which completes the biosynthesis of the molecule. The cysteine-adding step is assumed to be carried out by the enzyme BshC on the basis of
genetic knockout studies, but the activity of BshC has not been observed in vitro.[5][7]
^
abS. V. Sharma; V. K. Jothivasan; G. L. Newton; H. Upton; J. I.Wakabayashi; M. G. Kane; A. A. Roberts; M. Rawat; J. J. La Clair & C. J. Hamilton. (July 2011). "Chemical and Chemoenzymatic Syntheses of Bacillithiol: A Unique Low-Molecular-Weight Thiol amongst Low G + C Gram-Positive Bacteria". Angew. Chem. Int. Ed. 50 (31): 7101–7104.
doi:
10.1002/anie.201100196.
PMID21751306.