Skip to main content
SpringerLink
Log in

Biosynthesis of clavam metabolites

  • Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Naturally occurring clavam metabolites include the valuable β-lactamase inhibitor, clavulanic acid, as well as stereochemical variants with side-chain modifications, called the 5S clavams. Because of the clinical importance of clavulanic acid, most studies of clavam biosynthesis are based on the industrial producer species Streptomyces clavuligerus. Well-characterized early steps in clavam biosynthesis are outlined, and less well understood late steps in 5S clavam biosynthesis are proposed. The complex genetic organization of the clavam biosynthetic genes in S. clavuligerus is described and, where possible, comparisons with other producer species are presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ARE:

Autoregulatory element

BLIP:

Beta-lactamase inhibitor protein

BLS:

β-lactam synthetase

CAD:

Clavaldehyde dehydrogenase

CAS:

Clavaminic acid synthase

CcaR:

Cephamycin and clavulanic acid regulator

CEAS:

Carboxyethylarginine synthase

CYP:

Cytochrome P450

FD:

Ferredoxin

GCAS:

Glycylclavaminic acid synthase

OAT:

Ornithine acetyltransferase

OPP:

Oligopeptide permease

PAH:

Proclavaminic acid amidinohydrolase

PBP:

Penicillin-binding protein

SARP:

Streptomyces antibiotic regulatory protein

References

  1. Aidoo KA, Wong A, Alexander DC, Rittammer RA, Jensen SE (1994) Cloning, sequencing and disruption of a gene from Streptomyces clavuligerus involved in clavulanic acid biosynthesis. Gene 147:41–46

    Article  PubMed  CAS  Google Scholar 

  2. Alexander DC, Jensen SE (1998) Investigation of the Streptomyces clavuligerus cephamycin C gene cluster and its regulation by the CcaR protein. J Bacteriol 180:4068–4079

    PubMed  CAS  Google Scholar 

  3. Anton N, Mendes MV, Martin JF, Aparicio JF (2004) Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis. J Bacteriol 186:2567–2575

    Article  PubMed  CAS  Google Scholar 

  4. Arulanantham H, Kershaw NJ, Hewitson KS, Hughes CE, Thirkettle JE, Schofield CJ (2006) ORF17 from the clavulanic acid biosynthesis gene cluster catalyzes the ATP-dependent formation of N-glycyl-clavaminic acid. J Biol Chem 281:279–287

    Article  PubMed  CAS  Google Scholar 

  5. Bachmann BO, Li R, Townsend CA (1998) β-Lactam synthetase: a new biosynthetic enzyme. Proc Natl Acad Sci USA 95:9082–9086

    Article  PubMed  CAS  Google Scholar 

  6. Baggaley KH, Brown AG, Schofield CJ (1997) Chemistry and biosynthesis of clavulanic acid and other clavams. Nat Prod Rep 14:309–333

    Article  PubMed  CAS  Google Scholar 

  7. Baldwin JE, Lloyd MD, Wha-Son B, Schofield CJ, Elson SW, Baggaley KH, Nicholson NH (1993) A substrate analog study on clavaminic acid synthase: possible clues to the biosynthetic origin of proclavaminic acid. J Chem Soc, Chem Commun 1993:500–502

    Article  Google Scholar 

  8. Bignell DR, Warawa JL, Strap JL, Chater KF, Leskiw BK (2000) Study of the bldG locus suggests that an anti-anti-sigma factor and an anti-sigma factor may be involved in Streptomyces coelicolor antibiotic production and sporulation. Microbiology 146:2161–2173

    PubMed  CAS  Google Scholar 

  9. Bignell DRD, Tahlan K, Colvin KR, Jensen SE, Leskiw BK (2005) Expression of ccaR, encoding the positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus, is dependent on bldG. Antimicrob Agents Chemother 49:1529–1541

    Article  PubMed  CAS  Google Scholar 

  10. Brown AG, Butterworth D, Cole M, Hanscombe G, Hood JD, Reading C, Robinson GN (1976) Naturally occurring beta-lactamase inhibitors with antibacterial activity. J Antibiot 29:668–669

    Article  PubMed  CAS  Google Scholar 

  11. Brown D, Evans JR, Fletton RA (1979) Structures of three novel β-lactams isolated from Streptomyces clavuligerus. J Chem Soc, Chem Commun 1979:282–283

    Article  Google Scholar 

  12. Caines MEC, Elkins JM, Hewitson KS, Schofield CJ (2004) Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway. J Biol Chem 279:5685–5692

    Article  PubMed  CAS  Google Scholar 

  13. de la Fuente A, Martin JF, Rodriguez-Garcia A, Liras P (2004) Two proteins with ornithine acetyltransferase activity show different functions in Streptomyces clavuligerus: oat2 modulates clavulanic acid biosynthesis in response to arginine. J Bacteriol 186:6501–6507

    Article  PubMed  Google Scholar 

  14. Demain AL, Elander RP (1999) The beta-lactam antibiotics: past, present, and future. Antonie Van Leeuwenhoek 75:5–19

    Article  PubMed  CAS  Google Scholar 

  15. Egan LA, Busby RW, IwataReuyl D, Townsend CA (1997) 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

    Article  CAS  Google Scholar 

  16. Elander RP (2003) Industrial production of beta-lactam antibiotics. Appl Microbiol Biotechnol 61:385–392

    PubMed  CAS  Google Scholar 

  17. Elkins JM, Kershaw NJ, Schofield CJ (2005) X-ray crystal structure of ornithine acetyltransferase from the clavulanic acid biosynthesis gene cluster. Biochem J 385:565–573

    Article  PubMed  CAS  Google Scholar 

  18. Elson SW, Gillett J, Nicholson NH, Tyler JW (1988) N-acyl derivatives of clavaminic acid produced by a mutant of Streptomyces clavuligerus. J Chem Soc, Chem Commun 1988:979–980

    Article  Google Scholar 

  19. Folcher M, Gaillard H, Nguyen LT, Nguyen KT, Lacroix P, Bamas-Jacques N, Rinkel M, Thompson CJ (2001) Pleiotropic functions of a Streptomyces pristinaespiralis autoregulator receptor in development, antibiotic biosynthesis, and expression of a superoxide dismutase. J Biol Chem 276:44297–44306

    Article  PubMed  CAS  Google Scholar 

  20. Goomeshi Nobary S, Jensen SE (2012) A comparison of the clavam biosynthetic gene clusters in Streptomyces antibioticus Tü1718 and Streptomyces clavuligerus. Can J Microbiol 58:413–425

    Article  PubMed  CAS  Google Scholar 

  21. Hara O, Beppu T (1982) Mutants blocked in streptomycin production in Streptomyces griseus—the role of A-factor. J Antibiot 35:349–358

    Article  PubMed  CAS  Google Scholar 

  22. Hashimoto K, Nihira T, Yamada Y (1992) Distribution of virginiae butanolides and IM-2 in the genus Streptomyces. J Ferment Bioeng 73:61–65

    Article  CAS  Google Scholar 

  23. Hodgson JE, Fosberry AP, Rawlinson NS, Ross HNM, Neal RJ, Arnell JC, Earl AJ, Lawlor EJ (1995) Clavulanic acid biosynthesis in Streptomyces clavuligerus: gene cloning and characterization. Gene 166:49–55

    Article  PubMed  CAS  Google Scholar 

  24. Howarth TT, Brown AG, King TJ (1976) Clavulanic acid, a novel β-lactam isolated from Streptomyces clavuligerus; X-ray crystal structure analysis. J Chem Soc Chem Commun 1976:266b–267b

  25. Iqbal A, Arunlanantham H, Brown T Jr, Chowdhury R, Clifton IJ, Kershaw NJ, Hewitson KS, McDonough MA, Schofield CJ (2010) Crystallographic and mass spectrometric analyses of a tandem GNAT protein from the clavulanic acid biosynthesis pathway. Proteins 78:1398–1407

    PubMed  CAS  Google Scholar 

  26. Jensen SE, Paradkar AS, Mosher RH, Anders C, Beatty PH, Brumlik MJ, Griffin A, Barton B (2004) Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. Antimicrob Agents Chemother 48:192–202

    Article  PubMed  CAS  Google Scholar 

  27. Jensen SE, Wong A, Griffin A, Barton B (2004) Streptomyces clavuligerus has a second copy of the proclavaminate amidinohydrolase gene. Antimicrob Agents Chemother 48:514–520

    Article  PubMed  CAS  Google Scholar 

  28. Jensen SE, Elder KJ, Aidoo KA, Paradkar AS (2000) Enzymes catalyzing the early steps of clavulanic acid biosynthesis are encoded by two sets of paralogous genes in Streptomyces clavuligerus. Antimicrob Agents Chemother 44:720–726

    Article  PubMed  CAS  Google Scholar 

  29. Jensen SE, Paradkar AS (1999) Biosynthesis and molecular genetics of clavulanic acid. Antonie Leeuwenhoek 75:125–133

    Article  PubMed  CAS  Google Scholar 

  30. Kershaw NJ, McNaughton HJ, Hewitson KS, Hernandez H, Griffin J, Hughes C, Greaves P, Barton B, Robinson CV, Schofield CJ (2002) ORF6 from the clavulanic acid gene cluster of Streptomyces clavuligerus has ornithine acetyltransferase activity. Eur J Biochem 269:2052–2059

    Article  PubMed  CAS  Google Scholar 

  31. Khaleeli N, Li RF, Townsend CA (1999) Origin of the β-lactam carbons in clavulanic acid from an unusual thiamine pyrophosphate-mediated reaction. J Am Chem Soc 121:9223–9224

    Article  CAS  Google Scholar 

  32. Khokhlov AS, Tovarova II, Borisova LN, Pliner SA, Shevchenko LN, Kornitskaia EI, Ivkina NS, Rapoport IA (1967) The A-factor, responsible for streptomycin biosynthesis by mutant strains of Actinomyces streptomycini. Dokl Akad Nauk SSSR 177:232–235

    PubMed  CAS  Google Scholar 

  33. Kim HS, Lee YJ, Lee CK, Choi SU, Yeo SH, Hwang YI, Yu TS, Kinoshita H, Nihira T (2004) Cloning and characterization of a gene encoding the gamma-butyrolactone autoregulator receptor from Streptomyces clavuligerus. Arch Microbiol 182:44–50

    Article  PubMed  CAS  Google Scholar 

  34. Kinoshita H, Tsuji T, Ipposhi H, Nihira T, Yamada Y (1999) Characterization of binding sequences for butyrolactone autoregulator receptors in streptomycetes. J Bacteriol 181:5075–5080

    PubMed  CAS  Google Scholar 

  35. Kwong T, Zelyas NJ, Cai H, Tahlan K, Wong A, Jensen SE (2012) 5S clavam biosynthesis is controlled by an atypical two-component regulatory system in Streptomyces clavuligerus. Antimicrob Agents Chemother 56:4845–4855

    Google Scholar 

  36. Li R, Khaleeli N, Townsend CA (2000) Expansion of the clavulanic acid gene cluster: identification and in vivo functional analysis of three new genes required for biosynthesis of clavulanic acid by Streptomyces clavuligerus. J Bacteriol 182:4087–4095

    Article  PubMed  CAS  Google Scholar 

  37. Liras P, Santamarta I, Perez-Redondo R (2011) Clavulanic acid and clavams biosynthesis and regulation. In: Dyson P (ed) Streptomyces: molecular biology and biotechnology. Caister Academic Press, Wymondham, UK, pp 167–178

    Google Scholar 

  38. Liras P, Gomez-Escribano JP, Santamarta I (2008) Regulatory mechanisms controlling antibiotic production in Streptomyces clavuligerus. J Ind Microbiol Biotechnol 35:667–676

    Article  PubMed  CAS  Google Scholar 

  39. Liu G, Tian Y, Yang H, Tan H (2005) A pathway-specific transcriptional regulatory gene for nikkomycin biosynthesis in Streptomyces ansochromogenes that also influences colony development. Mol Microbiol 55:1855–1866

    Article  PubMed  CAS  Google Scholar 

  40. Lopez-Garcia MT, Santamarta I, Liras P (2010) Morphological differentiation and clavulanic acid formation are affected in a Streptomyces clavuligerus adpA-deleted mutant. Microbiology 156:2354–2365

    Article  PubMed  CAS  Google Scholar 

  41. Lorenzana LM, Pérez-Redondo R, Santamarta I, Martín JF, Liras P (2004) Two oligopeptide-permease-encoding genes in the clavulanic acid cluster of Streptomyces clavuligerus are essential for production of the β-lactamase inhibitor. J Bacteriol 186:3431–3438

    Article  PubMed  CAS  Google Scholar 

  42. Mackenzie AK, Valegard K, Iqbal A, Caines ME, Kershaw NJ, Jensen SE, Schofield CJ, Andersson I (2010) Crystal structures of an oligopeptide-binding protein from the biosynthetic pathway of the beta-lactamase inhibitor clavulanic acid. J Mol Biol 396:332–344

    Article  PubMed  CAS  Google Scholar 

  43. MacKenzie AK, Kershaw NJ, Hernandez H, Robinson CV, Schofield CJ, Andersson I (2007) Clavulanic acid dehydrogenase: structural and biochemical analysis of the final step in the biosynthesis of the beta-lactamase inhibitor clavulanic acid. Biochemistry 46:1523–1533

    Article  PubMed  CAS  Google Scholar 

  44. Marsh EN, Chang MD, Townsend CA (1992) Two isozymes of clavaminate synthase central to clavulanic acid formation: cloning and sequencing of both genes from Streptomyces clavuligerus. Biochemistry 31:12648–12657

    Article  PubMed  CAS  Google Scholar 

  45. McNaughton HJ, Thirkettle JE, Zhang ZH, Schofield CJ, Jensen SE, Barton B, Greaves P (1998) β-lactam synthetase: implications for β-lactamase evolution. Chem Commun 1998:2325–2326

    Article  Google Scholar 

  46. Medema MH, Trefzer A, Kovalchuk A, van den Berg M, Muller U, Heijne W, Wu L, Alam MT, Ronning CM, Nierman WC, Bovenberg RA, Breitling R, Takano E (2010) The sequence of a 1.8-mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways. Genome Biol Evol 2:212–224

    Article  PubMed  Google Scholar 

  47. Mellado E, Lorenzana LM, Rodriguez-Saiz M, Diez B, Liras P, Barredo JL (2002) The clavulanic acid biosynthetic cluster of Streptomyces clavuligerus: genetic organization of the region upstream of the car gene. Microbiology 148:1427–1438

    PubMed  CAS  Google Scholar 

  48. Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC (2001) Structure of β-lactam synthetase reveals how to synthesize antibiotics instead of asparagine. Nat Struct Biol 8:684–689

    Article  PubMed  CAS  Google Scholar 

  49. Mosher RH, Paradkar AS, Anders C, Barton B, Jensen SE (1999) Genes specific for the biosynthesis of clavam metabolites antipodal to clavulanic acid are clustered with the gene for clavaminate synthase 1 in Streptomyces clavuligerus. Antimicrob Agents Chemother 43:1215–1224

    PubMed  CAS  Google Scholar 

  50. Nicholson NH, Baggaley KH, Cassels R, Davison M, Elson SW, Fulston M, Tyler JW, Woroniecki SR (1994) Evidence that the immediate biosynthetic precursor of clavulanic acid is its N-aldehyde analog. J Chem Soc, Chem Commun 1994:1281–1282

    Article  Google Scholar 

  51. Onaka H, Horinouchi S (1997) DNA-binding activity of the A-factor receptor protein and its recognition DNA sequences. Mol Microbiol 24:991–1000

    Article  PubMed  CAS  Google Scholar 

  52. Paradkar AS, Aidoo KA, Jensen SE (1998) A pathway-specific transcriptional activator regulates late steps of clavulanic acid biosynthesis in Streptomyces clavuligerus. Mol Microbiol 27:831–843

    Article  PubMed  CAS  Google Scholar 

  53. Paradkar AS, Aidoo KA, Wong A, Jensen SE (1996) Molecular analysis of a β-lactam resistance gene encoded within the cephamycin gene cluster of Streptomyces clavuligerus. J Bacteriol 178:6266–6274

    PubMed  CAS  Google Scholar 

  54. Paradkar AS, Jensen SE (1995) Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. J Bacteriol 177:1307–1314

    PubMed  CAS  Google Scholar 

  55. Parsons L, Bonander N, Eisenstein E, Gilson M, Kairys V, Orban J (2003) Solution structure and functional ligand screening of HI0719, a highly conserved protein from bacteria to humans in the YjgF/YER057c/UK114 family. Biochemistry 42:80–89

    Article  PubMed  CAS  Google Scholar 

  56. Perez-Llarena FJ, Liras P, Rodriguez-Garcia A, Martin JF (1997) A regulatory gene (ccaR) required for cephamycin and clavulanic acid production in Streptomyces clavuligerus: amplification results in overproduction of both β-lactam compounds. J Bacteriol 179:2053–2059

    PubMed  CAS  Google Scholar 

  57. Perez-Redondo R, Rodriguez-Garcia A, Martin JF, Liras P (1999) Deletion of the pyc gene blocks clavulanic acid biosynthesis except in glycerol-containing medium: evidence for two different genes in formation of the C3 unit. J Bacteriol 181:6922–6928

    PubMed  CAS  Google Scholar 

  58. Perez-Redondo R, Rodriguez-Garcia A, Martin JF, Liras P (1998) The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene. Gene 211:311–321

    Article  PubMed  CAS  Google Scholar 

  59. Pruess DL, Kellett M (1983) Ro-22-5417, a new clavam antibiotic from Streptomyces clavuligerus I. Discovery and biological activity. J Antibiot 36:208–212

    Article  PubMed  CAS  Google Scholar 

  60. Rohl F, Rabenhorst J, Zahner H (1987) Biological properties and mode of action of clavams. Arch Microbiol 147:315–320

    Article  PubMed  CAS  Google Scholar 

  61. Salowe SP, Krol WJ, Iwata-Reuyl D, Townsend CA (1991) Elucidation of the order of oxidations and identification of an intermediate in the multistep clavaminate synthase reaction. Biochemistry, NY 30:2281–2292

    Article  CAS  Google Scholar 

  62. Salowe SP, Marsh EN, Townsend CA (1990) Purification and characterization of clavaminate synthase from Streptomyces clavuligerus: an unusual oxidative enzyme in natural product biosynthesis. Biochemistry 29:6499–6508

    Article  PubMed  CAS  Google Scholar 

  63. Santamarta I, Lopez-Garcia MT, Kurt A, Nardiz N, Alvarez-Alvarez R, Perez-Redondo R, Martin JF, Liras P (2011) Characterization of DNA-binding sequences for CcaR in the cephamycin-clavulanic acid supercluster of Streptomyces clavuligerus. Mol Microbiol 81:968–981

    Article  PubMed  CAS  Google Scholar 

  64. Santamarta I, Pérez-Redondo R, Lorenzana LM, Martín JF, Liras P (2005) Different proteins bind to the butyrolactone receptor protein ARE sequence located upstream of the regulatory ccaR gene of Streptomyces clavuligerus. Mol Microbiol 56:824–835

    Article  PubMed  CAS  Google Scholar 

  65. Santamarta I, Rodriguez-Garcia A, Perez-Redondo R, Martin JF, Liras P (2002) CcaR is an autoregulatory protein that binds to the ccaR and cefD-cmcI promoters of the cephamycin C-clavulanic acid cluster in Streptomyces clavuligerus. J Bacteriol 184:3106–3113

    Article  PubMed  CAS  Google Scholar 

  66. Schmitz G, Downs DM (2004) Reduced transaminase B (IlvE) activity caused by the lack of yjgF is dependent on the status of threonine deaminase (IlvA) in Salmonella enterica serovar Typhimurium. J Bacteriol 186:803–810

    Article  PubMed  CAS  Google Scholar 

  67. Song JY, Jensen SE, Lee KJ (2010) Clavulanic acid biosynthesis and genetic manipulation for its overproduction. Appl Microbiol Biotechnol 88:659–669

    Article  PubMed  CAS  Google Scholar 

  68. Song JY, Jeong H, Yu DS, Fischbach MA, Park HS, Kim JJ, Seo JS, Jensen SE, Oh TK, Lee KJ, Kim JF (2010) Draft genome sequence of Streptomyces clavuligerus NRRL 3585, a producer of diverse secondary metabolites. J Bacteriol 192:6317–6318

    Article  PubMed  CAS  Google Scholar 

  69. Song JY, Kim ES, Kim DW, Jensen SE, Lee KJ (2009) A gene located downstream of the clavulanic acid gene cluster in Streptomyces clavuligerus ATCC 27064 encodes a putative response regulator that affects clavulanic acid production. J Ind Microbiol Biotechnol 36:301–311

    Article  PubMed  CAS  Google Scholar 

  70. Tahlan K, Anders C, Wong A, Mosher RH, Beatty PH, Brumlik MJ, Griffin A, Hughes C, Griffin J, Barton B, Jensen SE (2007) 5S clavam biosynthetic genes are located in both the clavam and paralog gene clusters in Streptomyces clavuligerus. Chem Biol 14:131–142

    Article  PubMed  CAS  Google Scholar 

  71. Tahlan K, Anders C, Jensen SE (2004) The paralogous pairs of genes involved in clavulanic acid and clavam metabolite biosynthesis are differently regulated in Streptomyces clavuligerus. J Bacteriol 186:6286–6297

    Article  PubMed  CAS  Google Scholar 

  72. Tahlan K, Park HU, Jensen SE (2004) Three unlinked gene clusters are involved in clavam metabolite biosynthesis in Streptomyces clavuligerus. Can J Microbiol 50:803–810

    Article  PubMed  CAS  Google Scholar 

  73. Trepanier NK, Jensen SE, Alexander DC, Leskiw BK (2002) The positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus is mistranslated in a bldA mutant. Microbiology 148:643–656

    PubMed  CAS  Google Scholar 

  74. Valentine BP, Bailey CR, Doherty A, Morris J, Elson SW, Baggaley KH, Nicholson NH (1993) Evidence that arginine is a later metabolic intermediate than ornithine in the biosynthesis of clavulanic acid by Streptomyces clavuligerus. J Chem Soc, Chem Commun 1993:1210–1211

    Article  Google Scholar 

  75. Ward JM, Hodgson JE (1993) The biosynthetic genes for clavulanic acid and cephamycin production occur as a ‘super-cluster’ in three Streptomyces. FEMS Microbiol Lett 110:239–242

    Article  PubMed  CAS  Google Scholar 

  76. Wu TK, Busby RW, Houston TA, McIlwaine DB, Egan LA, Townsend CA (1995) Identification, cloning, sequencing, and overexpression of the gene encoding proclavaminate amidino hydrolase and characterization of protein function in clavulanic acid biosynthesis. J Bacteriol 177:3714–3720

    PubMed  CAS  Google Scholar 

  77. Zelyas NJ, Cai H, Kwong T, Jensen SE (2008) Alanylclavam biosynthetic genes are clustered together with one group of clavulanic acid biosynthetic genes in Streptomyces clavuligerus. J Bacteriol 190:7957–7965

    Article  PubMed  CAS  Google Scholar 

  78. Zhang Z, Ren J, Stammers DK, Baldwin JE, Harlos K, Schofield CJ (2000) Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat Struct Biol 7:127–133

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, University of Alberta, CW-405 Biological Sciences Building, Edmonton, AB, T6G 2E9, Canada

    Susan E. Jensen

Authors
  1. Susan E. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan E. Jensen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jensen, S.E. Biosynthesis of clavam metabolites. J Ind Microbiol Biotechnol 39, 1407–1419 (2012). https://doi.org/10.1007/s10295-012-1191-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-012-1191-0

Keywords

Search

Navigation