Increasing the success rate of lantibiotic drug discovery by Synthetic Biology

Expert Opinion on Drug Discovery

Volumn 7, Issue 8, 2012, Pages 695-709

  Montalbán López, Manuel ^a   Zhou, Liang ^a   Buivydas, Andrius ^a   Van Heel, Auke J ^a   Kuipers, Oscar P ^a,b  

^a UNIVERSITY OF GRONINGEN   (Netherlands)

^b Kluyver Center for Genomics of Industrial Fermentation   (Netherlands)

Author keywords

Antimicrobial; Genome mining; Lantibiotic; Post translational modification; Synthetic Biology

Indexed keywords

ACTAGARDIN; BACTERIOCIN; BOVICIN J50; EPIDERMIN; EPILANCIN K7; LACTICIN 3147; LACTOCIN S; LANTHIOPEPTIN; LANTIBIOTIC; MERSACIDIN; MICROBISPORICIN; NISIN; PAENIBACILLIN; PEP5; UNCLASSIFIED DRUG;

DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANTI-INFECTIVE AGENTS; BACTERIA; BACTERIOCINS; DRUG DISCOVERY; HUMANS; STRUCTURE-ACTIVITY RELATIONSHIP; SYNTHETIC BIOLOGY;

EID: 84864343905     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2012.693476     Document Type: Review

References (113)

1. Baquero F, Coque TM, De La Cruz F. Ecology and evolution as targets: The need for novel eco-evo drugs and strategies to fight antibiotic resistance. Antimicrob Agents Chemother 2011;55(8):3649-60
2. Fernandez L, Breidenstein EBM, Hancock REW. Creeping baselines and adaptive resistance to antibiotics. Drug Resist Updat 2011;14(1):1-21
3. Rivera AM, Boucher HW. Current concepts in antimicrobial therapy against select gram-positive organisms: Methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci, and vancomycin-resistant enterococci. Mayo Clin Proc 2011;86(12):1230-43
4. Vos MC, Behrendt MD, Melles DC, et al. 5 years of experience implementing a methicillin-resistant Staphylococcus aureus search and destroy policy at the largest university medical center in the Netherlands. Infect Control Hosp Epidemiol 2009;30(10):977-84
5. Graveland H, Wagenaar JA, Heesterbeek H, et al. Methicillin resistant Staphylococcus aureus ST398 in veal calf farming: Human MRSA carriage related with animal antimicrobial usage and farm hygiene. PLoS One 2010;5(6):e10990
6. Deleo FR, Otto M, Kreiswirth BN, Chambers HF. Community-associated methicillin-resistant Staphylococcus aureus. Lancet 2010;375(9725):1557-68
7. Harada K, Asai T. Role of antimicrobial selective pressure and secondary factors on antimicrobial resistance prevalence in Escherichia coli from food-producing animals in Japan. J Biomed Biotechnol 2010;2010:180682
8. Burrowes B, Harper DR, Anderson J, et al. Bacteriophage therapy: Potential uses in the control of antibiotic-resistant pathogens. Expert Rev Anti Infect Ther 2011;9(9):775-85
9. Boucher HW, Talbot GH, Bradley JS, et al. Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48(1):1-12
10. European Centre for Disease Prevention and Control/European Medicines Agency Joint technical report. The bacterial challenge: Time to react. 2009. DOI 10.2900/2518
11. The Lancet. Urgently needed: New antibiotics. Lancet 2009;374(9705):1868- 8
12. Spellberg B, Powers JH, Brass EP, et al. Trends in antimicrobial drug development: Implications for the future. Clin Infect Dis 2004;38(9):1279-86 (Pubitemid 38608571)
13. Willey JM, Van Der Donk WA. Lantibiotics: Peptides of diverse structure and function. Annu Rev Microbiol 2007;61:477-501 (Pubitemid 350058218)
14. Lubelski J, Rink R, Khusainov R, et al. Biosynthesis, immunity, regulation, mode of action and engineering of the model lantibiotic nisin. Cell Mol Life Sci 2008;65(3):455-76 (Pubitemid 351214649)
15. Bierbaum G, Sahl H-G. Lantibiotics: Mode of action, biosynthesis and bioengineering. Curr Pharm Biotechnol 2009;10(1):2-18
16. Kuipers OP, Bierbaum G, Ottenwalder B, et al. Protein engineering of lantibiotics. Antonie Van Leeuwenhoek 1996;69(2):161-9 (Pubitemid 26058494)
17. Kuipers OP, Rollema HS, Yap WM, et al. Engineering dehydrated amino acid residues in the antimicrobial peptide nisin. J Biol Chem 1992;267(34):24340-6
18. Chatterjee C, Paul M, Xie L, Van Der Donk WA. Biosynthesis and mode of action of lantibiotics. Chem Rev 2005;105(2):633-84
19. Velasquez JE, Van Der Donk WA. Genome mining for ribosomally synthesized natural products. Curr Opin Chem Biol 2011;15(1):11-21
20. Goto Y, Li B, Claesen J, et al. Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. PLoS Biol 2010;8(3):e1000339
21. Meindl K, Schmiederer T, Schneider K, et al. Labyrinthopeptins: A new class of carbacyclic lantibiotics. Angew Chem Int Ed Engl 2010;49(6):1151-4
22. Oman TJ, Van Der Donk WA. Follow the leader: The use of leader peptides to guide natural product biosynthesis. Nat Chem Biol 2010;6(1):9-18
23. Kuipers A, De Boef E, Rink R, et al. NisT, the transporter of the lantibiotic nisin, can transport fully modified, dehydrated, and unmodified prenisin and fusions of the leader peptide with non-lantibiotic peptides. J Biol Chem 2004;279(21):22176-82 (Pubitemid 38679411)
24. Rink R, Kluskens LD, Kuipers A, et al. NisC, the cyclase of the lantibiotic nisin, can catalyze cyclization of designed nonlantibiotic peptides. Biochemistry 2007;46(45):13179-89 (Pubitemid 350086236)
25. Rink R, Wierenga J, Kuipers A, et al. Production of dehydroamino acid-containing peptides by Lactococcus lactis. Appl Environ Microbiol 2007;73(6):1792-6 (Pubitemid 46449060)
26. Chatterjee C, Patton GC, Cooper L, et al. Engineering dehydro amino acids and thioethers into peptides using lacticin 481 synthetase. Chem Biol 2006;13(10):1109-17 (Pubitemid 44557075)
27. Kluskens LD, Kuipers A, Rink R, et al. Post-translational modification of therapeutic peptides by NisB, the dehydratase of the lantibiotic nisin. Biochemistry 2005;44(38):12827-34 (Pubitemid 41377322)
28. Levengood MR, Van Der Donk WA. Use of lantibiotic synthetases for the preparation of bioactive constrained peptides. Bioorg Med Chem Lett 2008;18(10):3025-8 (Pubitemid 351680395)
29. Breukink E, Wiedemann I, Van Kraaij C, et al. Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 1999;286(5448):2361-4 (Pubitemid 30016902)
30. Hasper HE, Kramer NE, Smith JL, et al. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II. Science 2006;313(5793):1636-7 (Pubitemid 44414037)
31. Pag U, Sahl H-G. Multiple activities in lantibiotics-models for the design of novel antibiotics? Curr Pharm Des 2002;8(9):815-33 (Pubitemid 34498567)
32. Kramer NE, Van Hijum SAFT, Knol J, et al. Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires nisin resistance. Antimicrob Agents Chemother 2006;50(5):1753-61
33. Jones T, Yeaman MR, Sakoulas G, et al. Failures in clinical treatment of Staphylococcus aureus Infection with daptomycin are associated with alterations in surface charge, membrane phospholipid asymmetry, and drug binding. Antimicrob Agents Chemother 2008;52(1):269-78
34. Patel D, Husain M, Vidaillac C, et al. Mechanisms of in-vitro-selected daptomycin-non-susceptibility in Staphylococcus aureus. Int J Antimicrob Agents 2011;38(5):442-6
35. Draper LA, Grainger K, Deegan LH, et al. Cross-immunity and immune mimicry as mechanisms of resistance to the lantibiotic lacticin 3147. Mol Microbiol 2009;71(4):1043-54
36. Mota-Meira M, LaPointe G, Lacroix C, Lavoie MC. MICs of mutacin B-Ny266, nisin A, vancomycin, and oxacillin against bacterial pathogens. Antimicrob Agents Chemother 2000;44(1):24-9 (Pubitemid 30010667)
37. Piper C, Draper LA, Cotter PD, et al. A comparison of the activities of lacticin 3147 and nisin against drug-resistant Staphylococcus aureus and Enterococcus species. J Antimicrob Chemother 2009;64(3):546-51
38. Van Heel AJ, Montalban-Lopez M, Kuipers OP. Evaluating the feasibility of lantibiotics as an alternative therapy against bacterial infections in humans. Expert Opin Drug Metab Toxicol 2011;7(6):675-80
39. Al-Mahrous MM, Upton M. Discovery and development of lantibiotics; antimicrobial agents that have significant potential for medical application. Expert Opin Drug Discov 2011;6(2):155-70
40. Montalban-Lopez M, Sanchez-Hidalgo M, Valdivia E, et al. Are bacteriocins underexploited? Novel applications for old antimicrobials. Curr Pharm Biotechnol 2011;12(8):1205-20
41. Rea MC, Sit CS, Clayton E, et al. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile. Proc Natl Acad Sci USA 2010;107(20):9352-7
42. Xiao H, Chen X, Chen M, et al. Bovicin HJ50, a novel lantibiotic produced by Streptococcus bovis HJ50. Microbiology (Reading, Engl.) 2004;150(Pt 1):103-8 (Pubitemid 38111475)
43. Muller WM, Ensle P, Krawczyk B, Sussmuth RD. Leader peptide-directed processing of labyrinthopeptin A2 precursor peptide by the modifying enzyme LabKC. Biochemistry 2011;50(39):8362-73
44. Castiglione F, Cavaletti L, Losi D, et al. A novel lantibiotic acting on bacterial cell wall synthesis produced by the uncommon actinomycete Planomonospora sp. Biochemistry 2007;46(20):5884-95 (Pubitemid 46799151)
45. Castiglione F, Lazzarini A, Carrano L, et al. Determining the structure and mode of action of microbisporicin, a potent lantibiotic active against multiresistant pathogens. Chem Biol 2008;15(1):22-31
46. De La Fuente R, Sonawane ND, Arumainayagam D, Verkman AS. Small molecules with antimicrobial activity against E. coli and P. aeruginosa identified by high-throughput screening. Br J Pharmacol 2006;149(5):551-9 (Pubitemid 44658516)
47. Ymele-Leki P, Cao S, Sharp J, et al. A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity. PLoS One 2012;7(2):e31307
48. Bosma T, Kuipers A, Bulten E, et al. Bacterial display and screening of posttranslationally thioether-stabilized peptides. Appl Environ Microbiol 2011;77(19):6794-801
49. Ramon-Garcia S, Ng C, Anderson H, et al. Synergistic drug combinations for tuberculosis therapy identified by a novel high-throughput screen. Antimicrob Agents Chemother 2011;55(8):3861-9
50. Stein T. Whole-cell matrix-assisted laser desorption/ionization mass spectrometry for rapid identification of bacteriocin/lantibiotic-producing bacteria. Rapid Commun Mass Spectrom 2008;22(8):1146-52 (Pubitemid 351600762)
51. Hindre T, Didelot S, Le Pennec J-P, et al. Bacteriocin detection from whole bacteria by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Appl Environ Microbiol 2003;69(2):1051-8 (Pubitemid 36204834)
52. Zendo T, Nakayama J, Fujita K, Sonomoto K. Bacteriocin detection by liquid chromatography/mass spectrometry for rapid identification. J Appl Microbiol 2008;104(2):499-507
53. Rose Sporns. McMullen. detection of bacteriocins by matrix-assisted laser Desorption/Ionization time-of-flight mass spectrometry. Appl Environ Microbiol 1999;65(5):2238-42
54. Kersten RD, Yang Y-L, Xu Y, et al. A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat Chem Biol 2011;7(11):794-802
55. Deegan LH, Suda S, Lawton EM, et al. Manipulation of charged residues within the two-peptide lantibiotic lacticin 3147. Microb Biotechnol 2010;3(2):222-34
56. Ross AC, Vederas JC. Fundamental functionality: Recent developments in understanding the structure-activity relationships of lantibiotic peptides. J Antibiot 2011;64(1):27-34
57. Field D, Collins B, Cotter PD, et al. A system for the random mutagenesis of the two-peptide lantibiotic lacticin 3147: Analysis of mutants producing reduced antibacterial activities. J Mol Microbiol Biotechnol 2007;13(4):226-34 (Pubitemid 47378152)
58. You YO, Van Der Donk WA. Mechanistic investigations of the dehydration reaction of lacticin 481 synthetase using site-directed mutagenesis. Biochemistry 2007;46(20):5991-6000 (Pubitemid 46799161)
59. Cotter PD, Deegan LH, Lawton EM, et al. Complete alanine scanning of the two-component lantibiotic lacticin 3147: Generating a blueprint for rational drug design. Mol Microbiol 2006;62(3):735-47 (Pubitemid 44571598)
60. Rink R, Wierenga J, Kuipers A, et al. Dissection and modulation of the four distinct activities of nisin by mutagenesis of rings A and B and by C-termina truncation. Appl Environ Microbiol 2007;73(18):5809-16 (Pubitemid 47462992)
61. Islam MR, Nishie M, Nagao J-I, et al. Ring A of Nukacin ISK-1: A Lipid II-Binding Motif for Type-A(II) Lantibiotic. J Am Chem Soc. 2012. Available from: Http://www.ncbi. nlm.nih.gov/pubmed/22329487. [Accedido febrero 28, 2012]
62. Van Der Meer JR, Rollema HS, Siezen RJ, et al. Influence of amino acid substitutions in the nisin leader peptide on biosynthesis and secretion of nisin by Lactococcus lactis. J Biol Chem 1994;269(5):3555-62 (Pubitemid 24237680)
63. Plat A, Kluskens LD, Kuipers A, et al. Requirements of the engineered leader peptide of nisin for inducing modification, export, and cleavage. Appl Environ Microbiol 2011;77(2):604-11
64. Rollema HS, Kuipers OP, Both P, et al. Improvement of solubility and stability of the antimicrobial peptide nisin by protein engineering. Appl Environ Microbiol 1995;61(8):2873-8
65. Field D, Connor PMO, Cotter PD, et al. The generation of nisin variants with enhanced activity against specific gram-positive pathogens. Mol. Microbiol 2008;69(1):218-30 (Pubitemid 351832767)
66. Rouse S, Field D, Daly KM, et al. Bioengineered nisin derivatives with enhanced activity in complex matrices. Microbial Biotechnol 2012. Available from: Http://www.ncbi. nlm.nih.gov/pubmed/22260415. [Accedido febrero 28, 2012]
67. Velasquez JE, Van Der Donk WA. Genome mining for ribosomally synthesized natural products. Curr Opin Chem Biol 2011;15(1):11-21
68. McClerren AL, Cooper LE, Quan C, et al. Discovery and in vitro biosynthesis of haloduracin, a two-component lantibiotic. Proc Natl Acad Sci USA 2006;103(46):17243-8 (Pubitemid 44788954)
69. Lawton EM, Cotter PD, Hill C, Ross RP. Identification of a novel two-peptide lantibiotic, haloduracin, produced by the alkaliphile Bacillus halodurans C-125. FEMS Microbiol. Lett 2007;267(1):64-71 (Pubitemid 46066541)
70. Dischinger J, Josten M, Szekat C, et al. Production of the novel two-peptide lantibiotic lichenicidin by Bacillus licheniformis DSM 13. Plos One 2009;4(8):e6788
71. Begley M, Cotter PD, Hill C, Ross RP. Identification of a novel two-peptide lantibiotic, lichenicidin, following rational genome mining for LanM proteins. Appl Environ Microbiol 2009;75(17):5451-60
72. De Jong A, Van Heel AJ, Kok J, Kuipers OP. BAGEL2: Mining for bacteriocins in genomic data. Nucleic Acids Res 2010;38(Web Server issue):W647-51
73. De Jong A, Van Hijum SAFT, Bijlsma JJE, et al. BAGEL: A web-based bacteriocin genome mining tool. Nucleic Acids Res 2006;34(Web Server issue):W273-9 (Pubitemid 44529778)
74. Hammami R, Zouhir A, Le Lay C, et al. BACTIBASE second release: A database and tool platform for bacteriocin characterization. BMC Microbiol 2010;10:22
75. Li B, Sher D, Kelly L, et al. Catalytic promiscuity in the biosynthesis of cyclic peptide secondary metabolites in planktonic marine cyanobacteria. Proc Natl Acad Sci USA 2010;107(23):10430-5
76. Wang H, Fewer DP, Sivonen K. Genome mining demonstrates the widespread occurrence of gene clusters encoding bacteriocins in cyanobacteria. PLoS ONE. 2011;6(7):e22384
77. Daly KM, Upton M, Sandiford SK, et al. Production of the Bsa lantibiotic by community-acquired Staphylococcus aureus strains. J Bacteriol 2010;192(4):1131-42
78. Marsh AJ, O'Sullivan O, Ross RP, et al. In silico analysis highlights the frequency and diversity of type 1 lantibiotic gene clusters in genome sequenced bacteria. BMC Genomics 2010;11(1):679
79. Nandagopal N, Elowitz MB. Synthetic biology: Integrated gene circuits. Science 2011;333(6047):1244-8
80. Majchrzykiewicz JA, Lubelski J, Moll GN, et al. Production of a class II two-component lantibiotic of Streptococcus pneumoniae using the class I nisin synthetic machinery and leader sequence. Antimicrob Agents Chemother 2010;54(4):1498-505
81. Caetano T, Krawczyk JM, Mosker E, et al. Heterologous expression, biosynthesis, and mutagenesis of type II lantibiotics from Bacillus licheniformis in Escherichia coli. Chem Biol 2011;18(1):90-100
82. Shi Y, Yang X, Garg N, Van Der Donk WA. Production of lantipeptides in Escherichia coli. J Am Chem Soc 2011;133(8):2338-41
83. Nagao J-I, Harada Y, Shioya K, et al. Lanthionine introduction into nukacin ISK-1 prepeptide by co-expression with modification enzyme NukM in Escherichia coli. Biochem Biophys Res Commun 2005;336(2):507-13 (Pubitemid 41267258)
84. Oldach F, Al Toma R, Kuthning A, et al. Congeneric lantibiotics from ribosomal in vivo peptide synthesis with noncanonical amino acids. Angew Chem Int Ed Engl 2011. Available from: Http://www.ncbi. nlm.nih.gov/pubmed/22128014. [Accedido febrero 26, 2012]
85. Huisgen R, Grashey R, Sauer J. Chemistry of alkenes. Interscience; En: NEW York: 1964. p. 806-877
86. Kolb HC, Finn MG, Sharpless KB. Click chemistry: Diverse chemical function from a few good reactions. Angewandte Chemie Int Ed 2001;40(11):2004-21
87. Chiang Y-M, Chang S-L, Oakley BR, Wang CCC. Recent advances in awakening silent biosynthetic gene clusters and linking orphan clusters to natural products in microorganisms. Curr Opin Chem Biol 2011;15(1):137-43
88. Asaduzzaman SM, Sonomoto K. Lantibiotics: Diverse activities and unique modes of action. J Biosci Bioeng 2009;107(5):475-87
89. Kupke T, Kempter C, Jung G, Gotz F. Oxidative decarboxylation of peptides catalyzed by flavoprotein EpiD. Determination of substrate specificity using peptide libraries and neutral loss mass spectrometry. J Biol Chem 1995;270(19):11282-9
90. Suda S, Cotter PD, Hill C, Ross RP. Lacticin 3147 - biosynthesis, molecular analysis, immunity, bioengineering and applications. Curr Protein Pept Sci 2011. Available from: Http://www.ncbi.nlm.nih. gov/pubmed/21827422. [Accedido febrero 28, 2012]
91. Mammen M, Choi S, Whitesides GM. Polyvalent interactions in biological systems: Implications for design and use of multivalent ligands and inhibitors. Angewandte Chemie Int Ed 1998;37(20):2754-94 (Pubitemid 29008561)
92. Arnusch CJ, Bonvin AMJJ, Verel AM, et al. The vancomycin-nisin(1-12) hybrid restores activity against vancomycin resistant Enterococci. Biochemistry 2008;47(48):12661-3
93. Tabor AB. The challenge of the lantibiotics: Synthetic approaches to thioether-bridged peptides. Org Biomol Chem 2011;9(22):7606-28
94. Levengood MR, Knerr PJ, Oman TJ, Van Der Donk WA. In vitro mutasynthesis of lantibiotic analogues containing nonproteinogenic amino acids. J Am Chem Soc 2009;131(34):12024-5
95. Levengood MR, Kerwood CC, Chatterjee C, Van Der Donk WA. Investigation of the substrate specificity of lacticin 481 synthetase by using nonproteinogenic amino acids. Chembiochem 2009;10(5):911-19
96. Zhang X, Ni W, Van Der Donk WA. On the regioselectivity of thioether formation by lacticin 481 synthetase. Org Lett 2007;9(17):3343-6
97. Zhang X, Van Der Donk WA. On the substrate specificity of dehydration by lacticin 481 synthetase. J Am Chem Soc 2007;129(8):2212-13 (Pubitemid 46362518)
98. Goto Y, Iwasaki K, Torikai K, et al. Ribosomal synthesis of dehydrobutyrineand methyllanthionine-containing peptides. Chem Commun (Camb.) 2009(23):3419-21
99. Seebeck FP, Ricardo A, Szostak JW. Artificial lantipeptides from in vitro translations. Chem Commun (Camb.) 2011;47(21):6141-3
100. Mothia B, Appleyard AN, Wadman S, Tabor AB. Synthesis of peptides containing overlapping lanthionine bridges on the solid phase: An analogue of rings D and E of the lantibiotic nisin. Org Lett 2011;13(16):4216-19
101. Liu W, Chan ASH, Liu H, et al. Solid supported chemical syntheses of both components of the lantibiotic lacticin 3147. J Am Chem Soc 2011;133(36):14216- 19
102. Pattabiraman VR, Stymiest JL, Derksen DJ, et al. Multiple on-resin olefin metathesis to form ring-expanded analogues of the lantibiotic peptide, lacticin 3147 A2. Org Lett 2007;9(4):699-702
103. Harmsen RAG, Ghalit N, Kemmink J, et al. Alkene/alkane-bridged mimics of the lantibiotic nisin: Toward novel peptide-based antibiotics. Adv Exp Med Biol 2009;611:533-4
104. Liu H, Pattabiraman VR, Vederas JC. Synthesis and biological activity of oxa-lacticin A2, a lantibiotic analogue with sulfur replaced by oxygen. Org Lett 2009;11(24):5574-7
105. Papo N, Oren Z, Pag U, et al. The consequence of sequence alteration of an amphipathic alpha-helical antimicrobial peptide and its diastereomers. J Biol Chem 2002;277(37):33913-21
106. Okesli A, Cooper LE, Fogle EJ, Van Der Donk WA. Nine post-translational modifications during the biosynthesis of cinnamycin. J Am Chem Soc 2011;133(34):13753-60
107. Meyer HE, Heber M, Eisermann B, et al. Sequence analysis of lantibiotics: Chemical derivatization procedures allow a fast access to complete Edman degradation. Anal Biochem 1994;223(2):185-90 (Pubitemid 24368964)
108. Mørtvedt CI, Nissen-Meyer J, Sletten K, Nes IF. Purification and amino acid sequence of lactocin S, a bacteriocin produced by Lactobacillus sake L45. Appl Environ Microbiol 1991;57(6):1829-34
109. Van De Kamp M, Horstink LM, Van Den Hooven HW, et al. Sequence analysis by NMR spectroscopy of the peptide lantibiotic epilancin K7 from Staphylococcus epidermidis K7. Eur J Biochem 1995;227(3):757-71
110. Majer F, Schmid DG, Altena K, et al. The flavoprotein MrsD catalyzes the oxidative decarboxylation reaction involved in formation of the peptidoglycan biosynthesis inhibitor mersacidin. J Bacteriol 2002;184(5):1234-43 (Pubitemid 34157544)
111. Foulston LC, Bibb MJ. Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes. Proc Natl Acad Sci USA 2010;107(30):13461-6
112. Boakes S, Cortes J, Appleyard AN, et al. Organization of the genes encoding the biosynthesis of actagardine and engineering of a variant generation system. Mol Microbiol 2009;72(5):1126-36
113. He Z, Yuan C, Zhang L, Yousef AE. N-terminal acetylation in paenibacillin, a novel lantibiotic. FEBS Lett 2008;582(18):2787-92