New reactions in clavulanic acid biosynthesis

Current Opinion in Chemical Biology

Volumn 6, Issue 5, 2002, Pages 583-589

  Townsend, Craig A ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CEPHALOSPORIN DERIVATIVE; CLAVAMINATE SYNTHASE; CLAVULANIC ACID; PENICILLIN DERIVATIVE; SYNTHETASE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; BACTERIAL INFECTION; BIOSYNTHESIS; CHEMICAL REACTION; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; NONHUMAN; REACTION ANALYSIS; REVIEW;

BACTERIA (MICROORGANISMS);

EID: 0036801379     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(02)00392-7     Document Type: Review

References (44)

1. Reading C., Cole M. Clavulanic acid: a β-lactamase inhibiting beta lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother. 11:1977;852-857.
2. Baggaley K.H., Brown A.G., Schofield C.J. Chemistry and biosynthesis of clavulanic acid and other clavams. Nat Prod Rep. 14:1997;309-333.
3. Marsh E.N., Chang M.D.-T., Townsend C.A. Two isozymes of clavaminate synthase central to clavulanic acid formation: cloning and sequencing of both genes from Streptomyces clavuligerus. Biochemistry. 31:1992;12648-12657.
4. Solomon E.I., Brunold T.C., Davis M.I., Kemsley J.N., Lee S.-K., Lenert N., Neese F., Skulan A.J., Yang Y.-S., Zhou J. Geometric and electronic structure/function correlations in non-heme iron enzymes. Chem Rev. 100:2000;235-249. This review gives an authoritative overview of non-heme iron oxygenase structural features.
5. Ryle M.J., Hausinger R.P. Non-heme iron oxygenases. Curr Opin Chem Biol. 6:2002;193-201.
6. Bachmann B.O., Li R., Townsend C.A. β-Lactam synthetase: a new biosynthetic enzyme. Proc Natl Acad Sci USA. 95:1998;9082-9086.
7. McNaughton HJ, Thirkettle JE, Zhang Z, Schofield CJ, Jensen SE, Barton B, Greaves P: β-Lactam synthetase: Implications for β-lactamase evolution. J Chem Soc Chem Commun 1998:2325-2326.
8. Cane D.E. Biosynthesis meets bioinformatics. Science. 287:2000;818-819. In this 'Perspectives' article, incisive comments are made about the transition of biochemical thinking from the discovery of biochemical reactions to the functional decryption of gene sequence information.
9. Bailey C.R., Butler M.J., Normansell I.D., Rowland R.T., Winstanley D.J. Cloning a Streptomyces clavuligerus genetic locus involved in clavulanic acid biosynthesis. Biotechnology. 2:1984;808-811.
10. Jensen S.E., Alexander D.C., Paradkar A.S., Aidoo K.A. Extending the β-lactam biosynthetic gene cluster in Streptomyces clavuligerus. Baltz R.H., Hegeman G.D., Skatrud P.L., Industrial Microorganisms: Basic and Applied Molecular Genetics. 1993;169-176 American Society for Microbiology.
11. Hodgson J.E., Fosberry A.P., Rawlinson N.S., Ross H.N.M., Neal R.J., Arnell J.C., Earl A.J., Lawlor E.J. Clavulanic acid biosynthesis in Steptomyces clavuligerus: gene cloning and characterization. Gene. 166:1995;49-55.
12. Ward J.M., Hodgson J.E. The biosynthetic genes for clavulanic acid and cephamycin production occur as a 'super-cluster' in three Streptomyces. FEMS Microbiol Lett. 110:1993;239-242.
13. Townsend CA, Krol WJ: The role of molecular oxygen in clavulanic acid biosynthesis: evidence for a bacterial oxidative deamination. J Chem Soc Chem Commun 1988:1234-1236.
14. Krol W.J., Basak A., Salowe S.P., Townsend C.A. Oxidative cyclization chemistry catalyzed by clavaminate synthase. J Am Chem Soc. 111:1989;7625-7627.
15. Basak A., Salowe S.P., Townsend C.A. Stereochemical course of the key ring forming reactions in clavulanic acid biosynthesis. J Am Chem Soc. 112:1990;1654-1656.
16. Salowe S.P., Krol W.J., Iwata-Reuyl D., Townsend C.A. Elucidation of the order of oxidations and identification of an intermediate in the multistep clavaminate synthase reaction. Biochemistry. 30:1991;2281-2292.
17. McIlwaine DB, Townsend CA: Evidence for distinct mechanisms of monocyclic β-lactam biosynthesis. J Chem Soc Chem Commun 1993:1346-1347.
18. 2]-D,L- glycerate in clavulanic acid biosynthesis. J Chem Soc Chem Commun 1997:225-226.
19. Elson SW, Baggaley KH, Gillet J, Holland S, Nicholson NH, Sime JT, Woroniecki SR: Isolation of two novel intracellular β-lactams and a novel dioxygenase cyclising enzyme from Streptomyces clavuligerus. J Chem Soc Chem Commun 1987:1736-1738.
20. Salowe S.P., Marsh E.N., Townsend C.A. Purification and characterization of clavaminate synthase from Streptomyces clavuligerus: an unusual oxidative enzyme in natural product biosynthesis. Biochemistry. 29:1990;6499-6508.
21. Baldwin JE, Lloyd MD, Wha-Son B, Schofield CJ, Elson SW, Baggaley KH, Nicholson NH: A Substrate analogue study on clavaminic acid synthase: Possible clues to the biosynthetic origin of proclavaminic acid. J Chem Soc Chem Commun 1993:500-502.
22. Elson SW, Baggaley KH, Davison M, Fulston M, Nicholson NH, Risbridger GD, Tyler JW: The identification of three new biosynthetic intermediates and one further biosynthetic enzyme in the clavulanic acid pathway. J Chem Soc Chem Commun 1993:1212-1214.
23. Aidoo K.A., Wong A., Alexander D.C., Rittammer R.A.R., Jensen S.E. Cloning, sequencing and disruption of a gene from Streptomyces clavuligerus involved in clavulanic acid biosynthesis. Gene. 147:1994;41-46.
24. Wu T.K., Busby R.W., Houston T.A., McIlwaine D.B., Egan L.A., Townsend C.A. Identification, cloning, sequencing and over-expression of the gene encoding proclavaminate amidino hydrolase and characterization of protein function in clavulanic acid biosynthesis. J Bacteriol. 177:1995;3714-3720.
25. Busby R.W., Townsend C.A. A single monomeric iron center in clavaminate synthase catalyzes three nonsuccessive oxidative transformations. BioorgMed Chem. 4:1996;1059-1064.
26. Khaleeli N., Busby R.W., Townsend C.A. Site-directed mutagenesis and biochemical analysis of the endogenous ligands in the ferrous active site of clavaminate synthase. The His-3 variant of the 2-His-1-carboxylate model. Biochemistry. 39:2000;8666-8673. Histidine residues were mutagenized to glutamine rather than alanine in this study. Statistical analysis of naturally occurring mutations in protein families where function is preserved indicates that glutamine is one of the most frequent substitutions for histidine. All mutants gave detectable levels of normal catalytic activity, except two corresponding to histidine ligands to iron.
27. Que J.L., Ho R.Y.H. Dioxygen activation by enzymes with mononuclear non-heme iron active sites. Chem Rev. 96:1996;2607-2624.
28. Doan L.X., Hassan A., Lipscomb S.J., Dhanda A., Zhang Z., Schofield C.J. Mutagenesis studies on the iron binding ligands of clavaminate synthase. Biochem Biophys Res Commun. 279:2000;240-244.
29. Hogan D.A., Smith S.R., Saari E.A., McCracken J., Hausinger R.P. Site-directed mutagenesis of a 2,4-dichlorophenoxyacetic acid/α-ketoglutarate dioxygenase. J Biol Chem. 275:2000;12400-12409.
30. Pavel E.G., Zhou J., Busby R.W., Gunsior M., Townsend C.A., Solomon E.I. Circular dichroism and magnetic circular dichroism spectroscopic studies of the non-heme ferrous active site in clavaminate synthase and its interaction with α-ketoglutarate cosubstrate. J Am Chem Soc. 120:1998;743-753.
31. Zhou J., Gunsior M., Bachmann B.O., Townsend C.A., Solomon E.I. Substrate binding to the α-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: coupling mechanism and oxidatative decarboxylation and hydroxylation. J Am Chem Soc. 120:1998;13539-13540.
32. Zhang Z., Ren J., Stammers D.K., Baldwin J.E., Harlos K., Schofield C.J. Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat Struct Biol. 7:2000;127-133. These X-ray structures of CS1 with various substrates bound afford important insights into the function of α-KG-dependent non-heme iron oxygenases.
33. Zhang Z., Ren J., Harlos K., McKinnon C.H., Clifton I.J., Schofield C.J. Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal-centered rearrangements. FEBS Lett. 517:2002;7-12.
34. Zhou J., Kelly W.L., Bachmann B.O., Gunsior M., Townsend C.A., Solomon E.I. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: correlation with mechanisms and reactions. J Am Chem Soc. 123:2001;7388-7398. This paper advances a rationale to account for the alteration of the catalytic chemistry of CS between hydroxylation and oxidative cyclization/desaturation.
35. Richards N.G.L., Schuster S.M. Mechanistic issues in asparagine synthetase catalysis. Adv Enzymol Rel Areas Mol Biol. 72:1998;145-198.
36. Larsen T.M., Boehlein S.K., Schuster S.M., Richards N.G.L., Thoden J.B., Holden H.M., Rayment I. Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product. Biochemistry. 38:1999;16146-16157.
37. Zalkin H., Smith J.L. Enzymes utilizing glutamine as an amide donor. Adv Enzymol Rel Areas Mol Biol. 72:1998;87-144.
38. Bachmann B.O., Townsend C.A. Kinetic mechanism of the β-lactam synthetase of Streptomyces clavuligerus. Biochemistry. 39:2000;11187-11193.
39. Miller M.T., Bachmann B.O., Townsend C.A., Rosenzweig A.G. Structure of β-lactam synthetase reveals how to synthesize antibiotics instead of aspargine. Nat Struct Biol. 8:2001;684-689. The overall structural similarity of β-LS to AS-B is evident in this X-ray structure, but the more detailed changes are noteworthy that lead to a change in function and intramolecular acyl substitution to give β-lactam synthesis in this protein.
40. Bürgi H.B., Dunitz J.D. From crystal statics to chemical dynamics. Acc Chem Res. 16:1983;153-161.
41. Khaleeli N., Li R.-F., Townsend C.A. Origin of the β-lactam carbons in clavulanic acid from an unusual thiamine pyrophosphate-mediated reaction. J Am Chem Soc. 121:1999;9223-9224.
42. Townsend CA, Mao S-S: Clavulanic acid biosynthesis: The stereochemical course of β-lactam formation from chiral glycerol. J Chem Soc Chem Commun 1987:86-89.
43. 3 unit. J Am Chem Soc. 107:1985;1066-1068.
44. Gutman AL, Ribon V, Boltanski A: Incorporation of β-hydroxpropionate into the β-lactam residue of clavulanic acid. J Chem Soc Chem Commun 1985:1627-1629.