CylA is a sequence-specific protease involved in toxin biosynthesis

Oxford University Press (OUP) - Tập 46 Số 3-4 - Trang 537-549 - 2019
Weixin Tang1, Silvia C. Bobeica1, Li Wang2, Wilfred A. van der Donk1
10000 0004 1936 9991 grid.35403.31 Department of Chemistry Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign 600 S. Mathews Avenue 61801 Urbana IL USA
2grid.66859.34 Broad Institute of MIT and Harvard 02142 Cambridge MA USA

Tóm tắt

Abstract

CylA is a subtilisin-like protein belonging to a recently expanded serine protease family related to class II lanthipeptide biosynthesis. As a leader peptidase, CylA is responsible for maturation of the enterococcal cytolysin, a lantibiotic important for Enterococcus faecalis virulence. In vitro reconstitution of CylA reveals that it accepts both linear and modified cytolysin peptides with a preference for cyclized peptides. Further characterization indicates that CylA activates itself by removing its N-terminal 95 amino acids. CylA achieves sequence-specific traceless cleavage of non-cognate peptides even if they are post-translationally modified, which makes the peptidase a powerful tool for mining novel lanthipeptides by providing a general strategy for leader peptide removal. Knowledge about the substrate specificity of CylA may also facilitate the development of protease inhibitors targeting cytolysin biosynthesis as a potential therapeutic approach for enterococcal infections.

Từ khóa


Tài liệu tham khảo

Arnison, 2013, Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature, Nat Prod Rep, 30, 108, 10.1039/C2NP20085F

Bierbaum, 2009, Lantibiotics: mode of action, biosynthesis and bioengineering, Curr Pharm Biotechnol, 10, 2, 10.2174/138920109787048616

Bindman, 2013, A general method for fluorescent labeling of the N-termini of lanthipeptides and its application to visualize their cellular localization, J Am Chem Soc, 135, 10362, 10.1021/ja4010706

Booth, 1996, Structural analysis and proteolytic activation of Enterococcus faecalis cytolysin, a novel lantibiotic, Mol Microbiol, 21, 1175, 10.1046/j.1365-2958.1996.831449.x

Caetano, 2011, Heterologous expression, biosynthesis, and mutagenesis of type II lantibiotics from Bacillus licheniformis in Escherichia coli, Chem Biol, 18, 90, 10.1016/j.chembiol.2010.11.010

Cotter, 2005, Bacterial lantibiotics: strategies to improve therapeutic potential, Curr Protein Pept Sci, 6, 61, 10.2174/1389203053027584

Cox, 2005, Enterococcal cytolysin: a novel two component peptide system that serves as a bacterial defense against eukaryotic and prokaryotic cells, Curr Protein Pept Sci, 6, 77, 10.2174/1389203053027557

Daly, 2012, Lantibiotic production by pathogenic microorganisms, Curr Protein Pept Sci, 13, 509, 10.2174/138920312803582997

Dawson, 2000, Synthesis of native proteins by chemical ligation, Annu Rev Biochem, 69, 923, 10.1146/annurev.biochem.69.1.923

Dong, 2015, The enterococcal cytolysin synthetase has an unanticipated lipid kinase fold, eLife, 4, 07607, 10.7554/eLife.07607

Furgerson Ihnken, 2008, In vitro reconstitution and substrate specificity of a lantibiotic protease, Biochemistry, 47, 7352, 10.1021/bi800278n

Garg, 2012, Geobacillins: lantibiotics from Geobacillus thermodenitrificans, Proc Natl Acad Sci USA, 109, 5241, 10.1073/pnas.1116815109

Geissler, 1996, Serine protease EpiP from Staphylococcus epidermidis catalyzes the processing of the epidermin precursor peptide, J Bacteriol, 178, 284, 10.1128/jb.178.1.284-288.1996

Gibb, 2012, MALDIquant: a versatile R package for the analysis of mass spectrometry data, Bioinformatics, 28, 2270, 10.1093/bioinformatics/bts447

Gilmore, 1990, An HlyB-type function is required for expression of the Enterococcus faecalis hemolysin/bacteriocin, Infect Immun, 58, 3914, 10.1128/iai.58.12.3914-3923.1990

Goto, 2010, Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights, PLoS Biol, 8, e1000339, 10.1371/journal.pbio.1000339

Hetrick, 2017, Ribosomally synthesized and post-translationally modified peptide natural product discovery in the genomic era, Curr Opin Chem Biol, 38, 36, 10.1016/j.cbpa.2017.02.005

Knerr, 2012, Discovery, biosynthesis, and engineering of lantipeptides, Annu Rev Biochem, 81, 479, 10.1146/annurev-biochem-060110-113521

Kuhn, 2014, Structure and protective efficacy of the Staphylococcus aureus autocleaving protease EpiP, FASEB J, 28, 1780, 10.1096/fj.13-241737

Lawton, 2007, Identification of a novel two-peptide lantibiotic, Haloduracin, produced by the alkaliphile Bacillus halodurans C-125, FEMS Microbiol Lett, 267, 64, 10.1111/j.1574-6968.2006.00539.x

Li, 2009, In vitro studies of lantibiotic biosynthesis, Methods Enzymol, 458, 533, 10.1016/S0076-6879(09)04821-6

Li, 2006, Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis, Science, 311, 1464, 10.1126/science.1121422

Li, 2013, Commercial proteases: present and future, FEBS Lett, 587, 1155, 10.1016/j.febslet.2012.12.019

Lohans, 2014, Structure and biosynthesis of carnolysin, a homologue of enterococcal cytolysin with d-amino acids, J Am Chem Soc, 136, 13150, 10.1021/ja5070813

McClerren, 2006, Discovery and in vitro biosynthesis of haloduracin, a two-component lantibiotic, Proc Natl Acad Sci USA, 103, 17243, 10.1073/pnas.0606088103

Muir, 2003, Semisynthesis of proteins by expressed protein ligation, Annu Rev Biochem, 72, 249, 10.1146/annurev.biochem.72.121801.161900

Müller, 2010, In vitro biosynthesis of the prepeptide of type-III lantibiotic labyrinthopeptin A2 including formation of a C–C bond as a post-translational modification, Angew Chem Int Ed, 49, 2436, 10.1002/anie.200905909

Nishie, 2012, Antibacterial peptides “bacteriocins”: an overview of their diverse characteristics and applications, Biocontrol Sci, 17, 1, 10.4265/bio.17.1

Nishie, 2009, ATP-dependent leader peptide cleavage by NukT, a bifunctional ABC transporter, during lantibiotic biosynthesis, J Biosci Bioeng, 108, 460, 10.1016/j.jbiosc.2009.06.002

Ortega, 2015, Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB, Nature, 517, 509, 10.1038/nature13888

Ortega, 2014, Substrate specificity of the lanthipeptide peptidase ElxP and the oxidoreductase ElxO, ACS Chem Biol, 9, 1718, 10.1021/cb5002526

Plat, 2013, Mechanistic aspects of lanthipeptide leaders, Curr Protein Pept Sci, 14, 85, 10.2174/1389203711314020001

Power, 1986, Secretion and autoproteolytic maturation of subtilisin, Proc Natl Acad Sci USA, 83, 3096, 10.1073/pnas.83.10.3096

Repka, 2017, Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes, Chem Rev, 117, 5457, 10.1021/acs.chemrev.6b00591

Shi, 2011, Production of lantipeptides in Escherichia coli, J Am Chem Soc, 133, 2338, 10.1021/ja109044r

Tang, 2015, Applications of the class II lanthipeptide protease LicP for sequence-specific, traceless peptide bond cleavage, Chem Sci, 6, 6270, 10.1039/C5SC02329G

Tang, 2016, The enterococcal cytolysin synthetase coevolves with substrate for stereoselective lanthionine synthesis, ACS Chem Biol, 11, 2438, 10.1021/acschembio.6b00397

Tang, 2012, Structural characterization of four prochlorosins: a novel class of lantipeptides produced by planktonic marine cyanobacteria, Biochemistry, 51, 4271, 10.1021/bi300255s

Tang, 2013, The sequence of the enterococcal cytolysin imparts unusual lanthionine stereochemistry, Nat Chem Biol, 9, 157, 10.1038/nchembio.1162

Torres, 2015, Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism, Nat Commun, 6, 6204, 10.1038/ncomms7204

van der Meer, 1993, Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis, J Bacteriol, 175, 2578, 10.1128/jb.175.9.2578-2588.1993

Van Tyne, 2017, Raising the alarmone: within-host evolution of antibiotic-tolerant Enterococcus faecium, MBio, 8, e00066-17, 10.1128/mBio.00066-17

Van Tyne, 2013, Structure, function, and biology of the Enterococcus faecalis cytolysin, Toxins, 5, 895, 10.3390/toxins5050895

Völler, 2013, Involvement and unusual substrate specificity of a prolyl oligopeptidase in class III lanthipeptide maturation, J Am Chem Soc, 135, 7426, 10.1021/ja402296m

Walsh, 2014, Blurring the lines between ribosomal and nonribosomal peptide scaffolds, ACS Chem Biol, 9, 1653, 10.1021/cb5003587

Wang, 2014, Cerecidins, novel lantibiotics from Bacillus cereus with potent antimicrobial activity, Appl Environ Microbiol, 80, 2633, 10.1128/AEM.03751-13

Xu, 2014, Structure of the nisin leader peptidase NisP revealing a C-terminal autocleavage activity, Acta Crystallogr D Biol Crystallogr, 70, 1499, 10.1107/S1399004714004234

Yang, 2013, Ribosomally synthesized and post-translationally modified peptide natural products: new insights into the role of leader and core peptides during biosynthesis, Chem Eur J, 19, 7662, 10.1002/chem.201300401

Young, 2012, Recombinant protein expression and purification: a comprehensive review of affinity tags and microbial applications, Biotechnol J, 7, 620, 10.1002/biot.201100155