Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase.

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Ryan A Oliver, Rongfeng Li, Craig A Townsend

Author Information

Ryan A Oliver: Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland, USA. ORCID
Rongfeng Li: Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland, USA.
Craig A Townsend: Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland, USA. ORCID

PMID: 29155429 DOI: 10.1038/nchembio.2526

The N-sulfonated monocyclic ��-lactam ring characteristic of the monobactams confers resistance to zinc metallo-��-lactamases and affords the most effective class to combat carbapenem-resistant enterobacteria (CRE). Here we report unprecedented nonribosomal peptide synthetase activities, wherein an assembled tripeptide is N-sulfonated in trans before direct synthesis of the ��-lactam ring in a noncanonical, cysteine-containing thioesterase domain. This means of azetidinone synthesis is distinct from the three others known in nature.

PubChem-Substance | 347911495; 347911506; 347911517; 347911522; 347911523; 347911524; 347911525; 347911526; 347911527; 347911496; 347911497; 347911498; 347911499; 347911500; 347911501; 347911502; 347911503; 347911504; 347911505; 347911507; 347911508; 347911509; 347911510; 347911511; 347911512; 347911513; 347911514; 347911515; 347911516; 347911518; 347911519; 347911520; 347911521

Nat Prod Rep. 2008 Aug;25(4):757-93 [PMID: 18663394]
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E653-61 [PMID: 23382230]
Curr Opin Chem Biol. 2016 Dec;35:97-108 [PMID: 27693891]
Curr Opin Struct Biol. 2016 Dec;41:46-53 [PMID: 27289043]
Science. 1999 Apr 16;284(5413):486-9 [PMID: 10205056]
Nature. 2015 Apr 16;520(7547):383-7 [PMID: 25624104]
Nucleic Acids Res. 2015 Jan;43(Database issue):D222-6 [PMID: 25414356]
J Am Chem Soc. 2009 Nov 11;131(44):16033-5 [PMID: 19835378]
Trends Mol Med. 2012 May;18(5):263-72 [PMID: 22480775]
Methods Enzymol. 2009;458:181-217 [PMID: 19374984]
Nat Chem Biol. 2014 Apr;10(4):251-8 [PMID: 24531841]
Angew Chem Int Ed Engl. 2009;48(26):4688-716 [PMID: 19514004]
Biochemistry. 1998 Feb 10;37(6):1585-95 [PMID: 9484229]
Biochem Soc Trans. 2016 Jun 15;44(3):738-44 [PMID: 27284036]
Nature. 2015 May 7;521(7550):105-9 [PMID: 25686610]
Chem Biol. 2014 Mar 20;21(3):379-88 [PMID: 24485762]
Curr Opin Chem Biol. 2001 Oct;5(5):525-34 [PMID: 11578925]
Biochem J. 1980 Feb 15;186(2):613-6 [PMID: 7378068]
Nat Rev Microbiol. 2015 Jan;13(1):42-51 [PMID: 25435309]
Nat Prod Rep. 2012 Oct;29(10):1074-98 [PMID: 22802156]
J Biol Chem. 2011 Apr 22;286(16):14445-54 [PMID: 21357626]
Cell Chem Biol. 2017 Jan 19;24(1):24-34 [PMID: 28017601]

R01 AI014937/NIAID NIH HHS
R01 AI121072/NIAID NIH HHS
R37 AI014937/NIAID NIH HHS
R56 AI014937/NIAID NIH HHS

Anti-Bacterial Agents

Carbapenem-Resistant Enterobacteriaceae

Catalytic Domain

Drug Resistance, Multiple, Bacterial

Monobactams

Peptide Biosynthesis, Nucleic Acid-Independent

Peptide Synthases

Pseudomonas

Stereoisomerism

Anti-Bacterial Agents

Monobactams

Peptide Synthases

non-ribosomal peptide synthase

sulfazecin

Journal Article

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Activity and Biocatalytic Potential of an Indolylamide Generating Thioesterase.Acyl Donor Stringency and Dehydroaminoacyl Intermediates in β-Lactam Formation by a Non-ribosomal Peptide Synthetase.Genome mining of sulfonated lanthipeptides reveals unique cyclic peptide sulfotransferases.Structure of a bound peptide phosphonate reveals the mechanism of nocardicin bifunctional thioesterase epimerase-hydrolase half-reactions.Competing off-loading mechanisms of meropenem from an l,d-transpeptidase reduce antibiotic effectiveness.Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the ��-Lactam Antibiotics.The structure of the monobactam-producing thioesterase domain of SulM forms a unique complex with the upstream carrier protein domain.Synthesis of functionalized 2,3-diaminopropionates and their potential for directed monobactam biosynthesis.The operon is a marker of C4-alkylated monobactam biosynthesis and responsible for (,)-diaminobutyrate production.Fluorescence Assessment of the AmpR-Signaling Network of to Exposure to β-Lactam Antibiotics.

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