# Bacillithiol

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{{chembox
| Verifiedfields = changed
| Watchedfields  = changed
| verifiedrevid  = 460421310
| Name           = Bacillithiol
| Reference      = 
| ImageFile      = Bacillithiol structure.svg
| ImageSize      = 200px
| ImageName      = Structure of bacillithiol
| IUPACName      = (2''S'')-2-[2-(<small>L</small>-Cysteinamido)-2-deoxy-α-<small>D</small>-glucopyranosyloxy]butanedioic acid
| SystematicName = (2''S'')-2-({(2''R'',3''R'',4''R'',5''S'',6''R'')-3-[(2''R'')-2-Amino-3-sulfanylpropanamido]-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl}oxy)butanedioic acid
| OtherNames     = 
| Section1       = {{Chembox Identifiers
| CASNo_Ref = {{cascite|changed|??}}
| CASNo = 1184928-91-3
| Abbreviations = BSH, Cys-GlcN-mal
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 61338
| PubChem = 42614123
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 24604693
| SMILES = C([C@@H]1[C@H]([C@@H]([C@H]([C@H](O1)O[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)O)O)O
| InChI = 1/C13H22N2O10S/c14-4(3-26)11(21)15-8-10(20)9(19)6(2-16)25-13(8)24-5(12(22)23)1-7(17)18/h4-6,8-10,13,16,19-20,26H,1-3,14H2,(H,15,21)(H,17,18)(H,22,23)/t4-,5-,6+,8+,9+,10+,13-/m0/s1
| InChIKey = UHNHELGKNQMNGF-AOQKXWSCBS
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C13H22N2O10S/c14-4(3-26)11(21)15-8-10(20)9(19)6(2-16)25-13(8)24-5(12(22)23)1-7(17)18/h4-6,8-10,13,16,19-20,26H,1-3,14H2,(H,15,21)(H,17,18)(H,22,23)/t4-,5-,6+,8+,9+,10+,13-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UHNHELGKNQMNGF-AOQKXWSCSA-N
}}
| Section2       = {{Chembox Properties
| Formula = C<sub>13</sub>H<sub>22</sub>N<sub>2</sub>O<sub>10</sub>S
| MolarMass = 398.39 g/mol
| MeltingPt = 
| Density = 1.629 g/mL
  }}
| Section3       = 
| Section4       = 
| Section5       = 
| Section6       = 
}}

'''Bacillithiol''' ('''BSH''' or '''Cys-GlcN-mal''') is a [thiol](/source/thiol) compound found in ''[Bacillus](/source/Bacillus)'' species.<ref name=Newton>{{Cite journal
| doi = 10.1038/nchembio.189
| issn = 1552-4450
| last1 = Newton
| volume = 5
| issue = 9 | first1 = G. L.
| pages = 625–627
| last2 = Rawat | first2 = M.
| last3 = La Clair | first3 = J. J.
| last4 = Jothivasan | first4 = V. K.
| last5 = Budiarto | first5 = T.
| last6 = Hamilton | first6 = C. J.
| last7 = Claiborne | first7 = A.
| last8 = Helmann | first8 = J. D.
| last9 = Fahey | first9 = R. C.
| title = Bacillithiol is an antioxidant thiol produced in Bacilli
| journal = Nature Chemical Biology
| year = 2009
| pmid = 19578333
| pmc = 3510479
}}</ref> It is likely involved in maintaining cellular redox balance and plays a role in microbial resistance to the antibiotic [fosfomycin](/source/fosfomycin).

==Structure==
Chemically, it is a glycoside formed between <small>L</small>-cysteinyl-<small>D</small>-glucosamine and [malic acid](/source/malic_acid). It was isolated and identified (as its bacillithiol-S-[bimane](/source/bimane) derivative) in 2009 from ''[Staphylococcus aureus](/source/Staphylococcus_aureus)'' and ''[Deinococcus radiodurans](/source/Deinococcus_radiodurans)'',<ref name=Newton/> although it was first detected in 2007, as an unidentified thiol in ''[Bacillus anthracis](/source/Bacillus_anthracis)''.<ref>{{Cite journal| first1 = I.
| last2 = Parsonage | first2 = D.
| last4 = Newton
| last3 = Paige
| last5 = Fahey | first3 = C. | first4 = L.
| last7 = Jackowski
| last8 = Mallett | first5 = C.
| last1 = Nicely
| last9 = Claiborne | first6 = R.
| last6 = Leonardi | first7 = S. | first8 = C. | first9 = A. 
| title = STRUCTURE OF THE TYPE III PANTOTHENATE KINASE FROM Bacillus anthracis AT 2.0 Å RESOLUTION: IMPLICATIONS FOR COENZYME A-DEPENDENT REDOX BIOLOGY 
| journal = Biochemistry 
| volume = 46
| issue = 11 
| pages = 3234–3245 
| date=Mar 2007 | issn = 0006-2960
| pmid = 17323930
| pmc = 2613803 
| doi = 10.1021/bi062299p
}}</ref> The naturally occurring free thiol form of bacillithiol has since been synthesised and characterised along with its biosynthetic precursors and its symmetrical disulfide.<ref name="pmid21751306">{{cite journal |author1=S. V. Sharma |author2=V. K. Jothivasan |author3=G. L. Newton |author4=H. Upton |author5=J. I.Wakabayashi |author6=M. G. Kane |author7=A. A. Roberts |author8=M. Rawat |author9=J. J. La Clair |author10=C. J. Hamilton.  |name-list-style=amp |title=Chemical and Chemoenzymatic Syntheses of Bacillithiol: A Unique Low-Molecular-Weight Thiol amongst Low G + C Gram-Positive Bacteria|journal=Angew. Chem. Int. Ed. |volume=50 |issue=31 |pages=7101–7104 |date=July 2011 |pmid=21751306 |doi=10.1002/anie.201100196}}</ref>

==Biological role==
Bacillithiol appears to participate in the sensing of [peroxide](/source/peroxide)s by ''Bacillus'',<ref>{{Cite journal| first1 = W.
| last2 = Soonsanga
| last3 = Helmann | first2 = S. | first3 = D. 
| title = A complex thiolate switch regulates the Bacillus subtilis organic peroxide sensor OhrR
| journal = Proceedings of the National Academy of Sciences
| last1 = Lee
| volume = 104
| issue = 21 
| pages = 8743–8748 
| date=May 2007 | issn = 0027-8424
| pmid = 17502599
| pmc = 1885573 
| doi = 10.1073/pnas.0702081104
| bibcode = 2007PNAS..104.8743L | doi-access = free
}}</ref> but may also substitute for [glutathione](/source/glutathione), which is the most common intracellular [thiol](/source/thiol) in eukaryotes and some bacteria.<ref name=Newton/> Some of the genes involved in the biosynthesis of bacillithiol were identified and characterised in 2010.<ref name="pmid20308541">{{cite journal |vauthors=Gaballa A, Newton GL, Antelmann H |title=Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=107 |issue=14 |pages=6482–6 |date=April 2010 |pmid=20308541 |doi=10.1073/pnas.1000928107 |pmc=2851989|bibcode = 2010PNAS..107.6482G |display-authors=etal|doi-access=free }}</ref> Bacteria engineered to be deficient in bacillithiol demonstrated increased sensitivity to various electrophilic [xenobiotic](/source/xenobiotic) compounds, including the antibiotic [fosfomycin](/source/fosfomycin), suggesting that in these organisms the mechanism of [fosfomycin resistance](/source/Fosfomycin) relies on the presence of bacillithiol.<ref name="pmid20308541"/> Furthermore, ''in vitro'' kinetic studies have established that bacillithiol is a preferred thiol substrate for the antibiotic resistance enzyme FosB.<ref name="pmid21751306" /><ref name="pmid23256780">{{cite journal |author1=A. A. Roberts |author2=S. V. Sharma |author3=A. W. Strankman |author4=S. R. Duran |author5=M. Rawat |author6=C. J. Hamilton.  |name-list-style=amp |title=Mechanistic studies of FosB: a divalent-metal-dependent bacillithiol-S-transferase that mediates fosfomycin resistance in Staphylococcus aureus|journal=Biochem. J. |volume=451 |issue=1 |pages=69–79 |date=July 2013 |pmid=23256780 |doi=10.1042/BJ20121541 |pmc=3960972}}</ref>

==Biosynthesis==
Bacillithiol is produced via the enzymes BshA, BshB, and BshC. BshA replaces the [UDP](/source/Uridine_diphosphate) group on [UDP-''N''-acetylglucosamine](/source/Uridine_diphosphate_N-acetylglucosamine) with an [<small>L</small>-malyl](/source/Malic_acid) group. BshB then removes the [acetyl group](/source/acetyl_group). <small>L</small>-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](/source/Gene_knockout), but the activity of BshC has not been observed ''in vitro''.<ref name="pmid20308541"></ref><ref name="BshCstr">{{cite journal |author1=A. J. VanDuienen |author2=K. R. Winchell |author3=P. D. Cook |name-list-style=amp |title=X-ray Crystallographic Structure of BshC, a Unique Enzyme Involved in Bacillithiol Biosynthesis|journal=Biochemistry |volume=541 |issue=2 |pages=100–103 |date=January 20, 2015 |pmid=25496067 |doi=10.1021/bi501394q |pmc=4303302}}</ref>

== See also ==
* [Mycothiol](/source/Mycothiol)

== References ==
{{reflist}}

Category:Thiols
Category:Propionamides
Category:Dicarboxylic acids
Category:Hexosamines

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Adapted from the Wikipedia article [Bacillithiol](https://en.wikipedia.org/wiki/Bacillithiol) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Bacillithiol?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.