Origins of the β-lactam rings in natural products

Journal of Antibiotics

Volumn 66, Issue 7, 2013, Pages 401-410

  Tahlan, Kapil ^a   Jensen, Susan E ^b  

^a MEMORIAL UNIVERSITY OF NEWFOUNDLAND   (Canada)

^b UNIVERSITY OF ALBERTA   (Canada)

Author keywords

carbapenem; cephalosporin; monobactam; nocardicin; penicillin; tabtoxin

Indexed keywords

AMOXICILLIN PLUS CLAVULANIC ACID; ANTIMALARIAL AGENT; ASPARTATE AMMONIA LIGASE; BETA LACTAM ANTIBIOTIC; CARBAPENEM DERIVATIVE; CEPHALOSPORIN C; CEPHALOSPORIN DERIVATIVE; CEPHAMYCIN; CLAVULANIC ACID; ISOPENICILLIN N; ISOPENICILLIN N SYNTHETASE; MONOBACTAM DERIVATIVE; NOCARDICIN A; PENICILLIN DERIVATIVE; SULFAZECIN; TABTOXIN; THIENAMYCIN;

ASPERGILLUS FUMIGATUS; CATALYSIS; CEPHALOSPORIUM ACREMONIUM; CYCLIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; LYSOBACTER; NUCLEOTIDE SEQUENCE; OXIDATION; PECTOBACTERIUM CAROTOVORUM; PENICILLIUM CHRYSOGENUM; PRIORITY JOURNAL; REVIEW; SCOPULARIOPSIS; STAPHYLOCOCCUS; STREPTOMYCES; STREPTOMYCES CLAVULIGERUS; XANTHOMONAS;

BETA-LACTAMS; BIOLOGICAL AGENTS; BIOSYNTHETIC PATHWAYS; EVOLUTION, MOLECULAR;

EID: 84881012253     PISSN: 00218820     EISSN: 18811469     Source Type: Journal    
DOI: 10.1038/ja.2013.24     Document Type: Review

References (92)

1. Elander, R. P. Industrial production of beta-lactam antibiotics. Appl. Microbiol. Biotechnol. 61, 385-392 (2003).
2. Liras, P. & Martin, J. F. Gene clusters for b-lactam antibiotics and control of their expression: why have clusters evolved, and from where did they originate? Int. Microbiol. 9, 10-19 (2006).
3. Hamed, R. B. et al. The enzymes of beta-lactam biosynthesis. Nat. Prod. Rep. 30, 21-107 (2013).
4. Liras, P. & Demain, A. L. Chapter 16. Enzymology of beta-lactam compounds with cephem structure produced by actinomycete. Methods Enzymol. 458, 401-429 (2009).
5. Kershaw, N. J., Caines, M. E., Sleeman, M. C. & Schofield, C. J. The enzymology of clavam and carbapenem biosynthesis. Chem. Commun. 2005, 4251-4263 (2005).
6. Liras, P., Santamarta, I. & Perez-Redondo, R. Clavulanic acid and clavams biosynthesis and regulation. in Streptomyces: Molecular Biology and Biotechnology (ed. Dyson, P.) 167-178 (Caister Academic Press, Wymondham, UK, 2011).
7. Jensen, S. E. Biosynthesis of clavam metabolites. J. Ind. Microbiol. Biotechnol. 39, 1407-1419 (2012).
8. Brown, A. G. Discovery and development of new b-lactam antibiotics. Pure Appl. Chem. 59, 475-484 (1987).
9. Fleming, A. On the antibacterial action of a Penicillium, with special reference to their use in the isolation of B. influenzae. Brit. J. Exp. Pathol. 10, 226-236 (1929).
10. Elander, R. P. Strain improvement and preservation of b-lactam-producing microorganisms. in Antibiotics Containing the Beta-Lactam Structure (eds Demain, A. L. & Solomon, N. A.) 97-146 (Springer-Verlag, Berlin, 1983).
11. Kitano, K. et al. Production of cephalosporin antibiotics by strains belonging to the genera Arachnomyces, Anixiopsis and Spiroidium. Agr. Biol. Chem. 38, 1761-1762 (1974).
12. Higgens, C. E., Hamill, R. L., Sands, T. H., Hoehn, M. M. & Davis, N. E. Letter: The occurrence of deacetoxycephalosporin C in fungi and streptomycetes. J. Antibiot. 27, 298-300 (1974).
13. Aoki, H. & Okuhara, M. Natural beta-lactam antibiotics. Annu. Rev. Microbiol. 34, 159-181 (1980).
14. Demain, A. L. & Elander, R. P. The beta-lactam antibiotics: past, present, and future. Antonie Van Leeuwenhoek 75, 5-19 (1999).
15. Ono, H., Nozaki, Y., Katayama, N. & Okazaki, H. Cephabacins, new cephem antibiotics of bacterial origin. I. Discovery and taxonomy of the producing organisms and fermentation. J. Antibiot. 37, 1528-1535 (1984).
16. Singh, P. D., Young, M. G., Johnson, J. H., Cimarusti, C. M. & Sykes, R. B. Bacterial production of 7-formamidocephalosporins. Isolation and structure determination. J. Antibiot. 37, 773-780 (1984).
17. Penalva, M. A., Moya, A., Dopazo, J. & Ramon, D. Sequences of isopenicillin N synthetase genes suggest horizontal gene transfer from prokaryotes to eukaryotes. Proc. Biol. Sci. 241, 164-169 (1990).
18. Jensen, P. R. Linking species concepts to natural product discovery in the post-genomic era. J. Ind. Microbiol. Biotechnol. 37, 219-224 (2010).
19. Cohen, G., Shiffman, D., Mevarech, M. & Aharonowitz, Y. Microbial isopenicillin N synthase genes: structure, function, diversity and evolution. Trends Biotechnol. 8, 105-111 (1990).
20. Weigel, B. J. et al. Cloning and expression in Escherichia coli of isopenicillin N synthetase genes from Streptomyces lipmanii and Aspergillus nidulans. J. Bacteriol. 170, 3817-3826 (1988).
21. Huffman, G. W. et al. Substrate specificity of isopenicillin N synthase. J. Med. Chem. 35, 1897-1914 (1992).
22. Roach, P. L. et al. Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation. Nature 387, 827-830 (1997).
23. Roach, P. L. et al. Anaerobic crystallisation of an isopenicillin N synthase.Fe(II).sub-strate complex demonstrated by X-ray studies. Eur. J. Biochem. 242, 736-740 (1996).
24. Roach, P. L. et al. Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature 375, 700-704 (1995).
25. Jensen, S. E., Westlake, D. W. & Wolfe, S. Cyclization of d-(L-a-aminoadipyl)-L-cysteinyl-D-valine to penicillins by cell-free extracts of Streptomyces clavuligerus. J. Antibiot. 35, 483-490 (1982).
26. Leskiw, B. K. et al. Cloning and nucleotide sequence determination of the isopenicillin N synthetase gene from Streptomyces clavuligerus. Gene 62, 187-196 (1988).
27. Samson, S. M. et al. Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium. Nature 318, 191-194 (1985).
28. Hollander, I. J., Shen, Y. Q., Heim, J., Demain, A. L. & Wolfe, S. A pure enzyme catalyzing penicillin biosynthesis. Science 224, 610-612 (1984).
29. Jayatilake, G. S., Huddleston, J. A. & Abraham, E. P. Conversion of isopenicillin N into penicillin N in cell-free extracts of Cephalosporium acremonium. Biochem. J. 194, 645-647 (1981).
30. Jones, D. T., Taylor, W. R. & Thornton, J. M. The rapid generation of mutation data matrices from protein sequences. Comput. Appl. Biosci. 8, 275-282 (1992).
31. Felsenstein, J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39, 783-791 (1985).
32. Tamura, K. et al. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731-2739 (2011).
33. Long, A. J. et al. Structural studies on the reaction of isopenicillin N synthase with the truncated substrate analogues delta-(L-alpha-aminoadipoyl)-L- cysteinyl-glycine and delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alanine. Biochemistry 44, 6619-6628 (2005).
34. Aharonowitz, Y., Cohen, G. & Martin, J. F. Penicillin and cephalosporin biosynthetic genes: structure, organization, regulation, and evolution. Annu. Rev. Microbiol. 46, 461-495 (1992).
35. Higgens, C. E. & Kastner, R. E. Streptomyces clavuligerus sp. nov., a b-lactam antibiotic producer. Int. J. Syst. Bacteriol. 21, 326-331 (1971).
36. Howarth, T. T., Brown, A. G. & King, T. J. Clavulanic acid, a novel b-lactam isolated from Streptomyces clavuligerus; X-ray crystal structure analysis. Chem. Commun. 1976, 266b-267b (1976).
37. Jamin, M., Wilkin, J. M. & Frere, J. M. Bacterial DD-transpeptidases and penicillin. Essays Biochem 29, 1-24 (1995).
38. Frere, J. M., Nguyen-Disteche, M., Coyette, J. & Joris, B. Mode of action: interaction with the penicillin binding proteins. in The Chemistry of b-Lactams (ed. Page, M. I.) 148-197 (Blackie Academic & Professional, Glasgow, 1992).
39. Waley, S. G. b-lactamase: mechanism of action. in The Chemistry of b-Lactams (ed. Page, M. I.) 199-228 (Blackie Academic & Professional, Glasgow, 1992).
40. Strynadka, N. C. et al. Molecular structure of the acyl-enzyme intermediate in b-lactam hydrolysis at 1.7 A resolution. Nature 359, 700-705 (1992).
41. Pratt, R. F. b-lactamase: inhibition. in The Chemistry of b-Lactams (ed. Page, M. I.) 229-271 (Blackie Academic & Professional, Glasgow, 1992).
42. Brown, R. P., Aplin, R. T. & Schofield, C. J. Inhibition of TEM-2 b-lactamase from Escherichia coli by clavulanic acid: observation of intermediates by electrospray ionization mass spectrometry. Biochemistry 35, 12421-12432 (1996).
43. Jensen, S. E. & Paradkar, A. S. Biosynthesis and molecular genetics of clavulanic acid. Antonie Van Leeuwenhoek 75, 125-133 (1999).
44. Brown, D., Evans, J. R. & Fletton, R. A. Structures of three novel b-lactams isolated from Streptomyces clavuligerus. Chem. Commun. 1979, 282-283 (1979).
45. Pruess, D. L. & Kellett, M. Ro-22-5417, a new clavam antibiotic from Streptomyces clavuligerus I. Discovery and biological activity. J. Antibiot. 36, 208-212 (1983).
46. Rohl, F., Rabenhorst, J. & Zahner, H. Biological properties and mode of action of clavams. Arch. Microbiol. 147, 315-320 (1987).
47. Janc, J. W., Egan, L. A. & Townsend, C. A. Emerging evidence for a shared biosynthetic pathway among clavulanic acid and the structurally diverse clavam metabolites. Bioorg. Med. Chem. Lett. 3, 2313-2316 (1993).
48. Egan, L. A., Busby, R. W., IwataReuyl, D. & Townsend, C. A. Probable role of clavaminic acid as the terminal intermediate in the common pathway to clavulanic acid and the antipodal clavam metabolites. J. Am. Chem. Soc. 119, 2348-2355 (1997).
49. Bachmann, B. O., Li, R. & Townsend, C. A. b-Lactam synthetase: a new biosynthetic enzyme. Proc. Natl Acad. Sci. USA 95, 9082-9086 (1998).
50. Bachmann, B. O. & Townsend, C. A. Kinetic mechanism of the b-lactam synthetase of Streptomyces clavuligerus. Biochemistry 39, 11187-11193 (2000).
51. McNaughton, H. J. et al. b-lactam synthetase: implications for b-lactamase evolution. Chem. Commun. 1998, 2325-2326 (1998).
52. Raber, M. L., Arnett, S. O. & Townsend, C. A. A conserved tyrosyl-glutamyl catalytic dyad in evolutionarily linked enzymes: carbapenam synthetase and beta-lactam synthetase. Biochemistry 48, 4959-4971 (2009).
53. Raber, M. L., Castillo, A., Greer, A. & Townsend, C. A. A conserved lysine in beta-lactam synthetase assists ring cyclization: implications for clavam and carbapenem biosynthesis. Chembiochem 10, 2904-2912 (2009).
54. Raber, M. L., Freeman, M. F. & Townsend, C. A. Dissection of the stepwise mechanism to beta-lactam formation and elucidation of a rate-determining conformational change in beta-lactam synthetase. J. Biol. Chem. 284, 207-217 (2009).
55. Miller, M. T., Bachmann, B. O., Townsend, C. A. & Rosenzweig, A. C. The catalytic cycle of b-lactam synthetase observed by X-ray crystallographic snapshots. Proc. Natl Acad. Sci. USA 99, 14752-14757 (2002).
56. Miller, M. T., Bachmann, B. O., Townsend, C. A. & Rosenzweig, A. C. Structure of b-lactam synthetase reveals how to synthesize antibiotics instead of asparagine. Nat. Struct. Biol. 8, 684-689 (2001).
57. Saw, J. H. et al. Encapsulated in silica: genome, proteome and physiology of the thermophilic bacterium Anoxybacillus flavithermus WK1. Genome Biol 9, R161 (2008).
58. Butterworth, D., Cole, M., Hanscomb, G. & Rolinson, G. N. Olivanic acids, a family of beta-lactam antibiotics with beta-lactamase inhibitory properties produced by Streptomyces species. I. Detection, properties and fermentation studies. J. Antibiot. 32, 287-294 (1979).
59. Kahan, J. S. et al. Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties. J. Antibiot. 32, 1-12 (1979).
60. Stapley, E. O. et al. Epithienamycins-novel beta-lactams related to thienamycin. I. Production and antibacterial activity. J. Antibiot. 34, 628-636 (1981).
61. Nunez, L. E., Mendez, C., Brana, A. F., Blanco, G. & Salas, J. A. The biosynthetic gene cluster for the beta-lactam carbapenem thienamycin in Streptomyces cattleya. Chem. Biol. 10, 301-311 (2003).
62. McGowan, S. J. et al. Analysis of bacterial carbapenem antibiotic production genes reveals a novel beta-lactam biosynthesis pathway. Mol. Microbiol. 22, 415-426 (1996).
63. Sleeman, M. C. & Schofield, C. J. Carboxymethylproline synthase (CarB), an unusual carbon-carbon bond-forming enzyme of the crotonase superfamily involved in carba-penem biosynthesis. J. Biol. Chem. 279, 6730-6736 (2004).
64. Gerratana, B., Stapon, A. & Townsend, C. A. Inhibition and alternate substrate studies on the mechanism of carbapenam synthetase from Erwinia carotovora. Biochemistry 42, 7836-7847 (2003).
65. Bodner, M. J. et al. Definition of the common and divergent steps in carbapenem beta-lactam antibiotic biosynthesis. Chembiochem 12, 2159-2165 (2011).
66. Miller, M. T., Gerratana, B., Stapon, A., Townsend, C. A. & Rosenzweig, A. C. Crystal structure of carbapenam synthetase (CarA). J. Biol. Chem. 278, 40996-41002 (2003).
67. Aoki, H., Sakai, H., Kohsaka, M., Konomi, T. & Hosoda, J. Nocardicin A, a new monocyclic beta-lactam antibiotic. I. Discovery, isolation and characterization. J. Antibiot. 29, 492-500 (1976).
68. Imada, A., Kitano, K., Kintaka, K., Muroi, M. & Asai, M. Sulfazecin and isosulfazecin, novel beta-lactam antibiotics of bacterial origin. Nature 289, 590-591 (1981).
69. Duke, S. O. & Dayan, F. E. Modes of action of microbially-produced phytotoxins. To x i n s 3, 1038-1064 (2011).
70. Funayama, S. et al. Cytotoxic alkaloids of Pachysandra terminalis. Biol. Pharm. Bull. 23, 262-264 (2000).
71. Aviles, E. & Rodriguez, A. D. Monamphilectine A, a potent antimalarial beta-lactam from marine sponge Hymeniacidon sp: isolation, structure, semisynthesis, and bioactivity. Org. Lett. 12, 5290-5293 (2010).
72. Takagi, M. & Shin-Ya, K. Construction of a natural product library containing secondary metabolites produced by actinomycetes. J. Antibiot. 65, 443-447 (2012).
73. Cundliffe, E. & Demain, A. L. Avoidance of suicide in antibiotic-producing microbes. J. Ind. Microbiol. Biotechnol. 37, 643-672 (2010).
74. Wencewicz, T. A. & Walsh, C. T. Pseudomonas syringae Self-Protection from Tabtoxinine-beta-Lactam by Ligase TblF and Acetylase Ttr. Biochemistry 51, 7712-7725 (2012).
75. Scannell, J. P. et al. Antimetabolites produced by microorganisms. XII (S)-alanyl-3-[alpha-(S)-chloro-3-(S)-hydroxy 2-oxo-3-azetidinylmethyl]-(S)- alanine, a new beta-lac-tam containing natural product. J. Antibiot. 28, 1-6 (1975).
76. 2] pyruvate into the b-lactam moiety. Helv. Chim. Acta 73, 476-482 (1990).
77. 13C NMR spectroscopy to identify its biosynthetic precursors. J. Biol. Chem. 262, 4994-4999 (1987).
78. 1-pool. Helv. Chim. Acta 70, 412-422 (1987).
79. Kinscherf, T. G. & Willis, D. K. The biosynthetic gene cluster for the beta-lactam antibiotic tabtoxin in Pseudomonas syringae. J. Antibiot. 58, 817-821 (2005).
80. Gunsior, M. et al. The biosynthetic gene cluster for a monocyclic beta-lactam antibiotic, nocardicin A. Chem. Biol. 11, 927-938 (2004).
81. Land, M. et al. Complete genome sequence of Actinosynnema mirum type strain (101). Stand. Genomic Sci. 1, 46-53 (2009).
82. Davidsen, J. M. & Townsend, C. A. In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A. Chem. Biol. 19, 297-306 (2012).
83. Alexander, D. C. & Jensen, S. E. Investigation of the Streptomyces clavuligerus cephamycin C gene cluster and its regulation by the CcaR protein. J. Bacteriol. 180, 4068-4079 (1998).
84. Townsend, C. A. & Brown, A. M. Biosynthetic studies of nocardicin A. J. Am. Chem. Soc. 103, 2813-2814 (1981).
85. Harada, S., Tsubotani, S., Ono, H. & Okazaki, H. Cephabacins, new cephem antibiotics of bacterial origin. II. Isolation and characterization. J. Antibiot. 37, 1536-1545 (1984).
86. King, H. D., Langharig, J. & Sanglier, J. J. Clavamycins, new clavam antibiotics from two variants of Streptomyces hygroscopicus. I. Taxonomy of the producing organisms, fermentation, and biological activities. J. Antibiot. 39, 510-515 (1986).
87. Elson, S. W. et al. Isolation of two novel intracellular b-lactams and a novel dioxygenase cyclising enzyme from Streptomyces clavuligerus. Chem. Commun. 1987, 1736-1738 (1987).
88. Bycroft, B. W., Maslen, C., Box, S. J., Brown, A. & Tyler, J. W. The biosynthetic implications of acetate and glutamate incorporation into (3R, 5R)-carbapenam-3-carboxylic acid and (5R)-carbapen-2-em-3-carboxylic acid by Serratia sp. J. Antibiot. 41, 1231-1242 (1988).
89. Sykes, R. B. et al. Monocyclic beta-lactam antibiotics produced by bacteria. Nature 291, 489-491 (1981).
90. Wells, J. S. et al. EM5400, a family of monobactam antibiotics produced by Agrobacterium radiobacter. I. Taxonomy, fermentation and biological properties. J. Antibiot. 35, 295-299 (1982).
91. Wells, J. S. et al. SQ 26, 180, a novel monobactam. I Taxonomy, fermentation and biological properties. J. Antibiot. 35, 184-188 (1982).
92. Kikuchi, T. & Uyeo, S. Studies on the alkaloids of Pachysandra terminalis Sieb. et Zucc. (6). Structure of pachystermine-A and-B, novel type alkaloids having beta-lactam ring system. Tetrahedron Lett. 6, 3473-3485 (1965).