TY - JOUR
T1 - Structure-Activity Relationships of the S-Linked Glycocin Sublancin
AU - Biswas, Subhanip
AU - Garcia De Gonzalo, Chantal V.
AU - Repka, Lindsay M.
AU - Van Der Donk, Wilfred A.
N1 - Funding Information:
*E-mail:vddonk@illinois.edu. ORCID Wilfred A. van der Donk: 0000-0002-5467-7071 Author Contributions W.A.v.d.D., S.B., and C.V.G.D.G. designed the study; S.B. and C.V.G.D.G. produced sublancin in E. coli; L.M.R. introduced the haloduracin leader peptide; and S.B. carried out all mutagenesis and bioactivity studies. Funding This work was supported by the Howard Hughes Medical Institute (to W.A.v.d.D.). C.V.G.D.G was supported by a National Institute of General Medical Sciences-National Institutes of Health Chemistry-Biology Interface Training Grant (Grant 5T32-GM070421). L.M.R. was supported by a grant from the National Institutes of Health (Grant F32 GM108275). A Bruker UltrafleXtreme MALDI TOF/TOF mass spectrometer was purchased in part with a grant from the National Institutes of Health (Grant S10 RR027109 A). Notes The authors declare no competing financial interest.
Funding Information:
This work was supported by the Howard Hughes Medical Institute (to W.A.v.d.D.). C.V.G.D.G was supported by a National Institute of General Medical Sciences-National Institutes of Health Chemistry-Biology Interface Training Grant (Grant 5T32-GM070421). L.M.R. was supported by a grant from the National Institutes of Health (Grant F32 GM108275). A Bruker UltrafleXtreme MALDI TOF/TOF mass spectrometer was purchased in part with a grant from the National Institutes of Health (Grant S10 RR027109 A).
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/15
Y1 - 2017/12/15
N2 - Sublancin is a 37-amino acid antimicrobial peptide belonging to the glycocin family of natural products. It contains two helices that are held together by two disulfide bonds as well as an unusual S-glucosidic linkage to a Cys in a loop connecting the helices. We report the reconstitution of the biosynthetic pathway to this natural product in Escherichia coli. This technology enabled the evaluation of the structure-activity relationships of the solvent-exposed residues in the helices. The biosynthetic machinery proved tolerant of changes in both helices, and the bioactivity studies of the resulting mutants show that two residues in helix B are important for bioactivity, Asn31 and Arg33.
AB - Sublancin is a 37-amino acid antimicrobial peptide belonging to the glycocin family of natural products. It contains two helices that are held together by two disulfide bonds as well as an unusual S-glucosidic linkage to a Cys in a loop connecting the helices. We report the reconstitution of the biosynthetic pathway to this natural product in Escherichia coli. This technology enabled the evaluation of the structure-activity relationships of the solvent-exposed residues in the helices. The biosynthetic machinery proved tolerant of changes in both helices, and the bioactivity studies of the resulting mutants show that two residues in helix B are important for bioactivity, Asn31 and Arg33.
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U2 - 10.1021/acschembio.7b00819
DO - 10.1021/acschembio.7b00819
M3 - Article
C2 - 29112373
AN - SCOPUS:85038557879
SN - 1554-8929
VL - 12
SP - 2965
EP - 2969
JO - ACS chemical biology
JF - ACS chemical biology
IS - 12
ER -