Streptomyces clavuligerus

Fermentation. The commercial P-lactam antibiotics which act as starting material for all of the cephalosporins ate produced by submerged fermentation. The organisms used for the commercial production of the penicillins and cephalosporins ate mutants of PenicU/in chTysogenum and Cephalosporium acremonium respectively (3,153,154). Both ate tme fungi (eucaryotes). In contrast, the cephamycins ate produced by certain species of procaryotic Streptomyces including Streptomyces clavuligerus and Streptomyces lipmanii (21,103). 

Other workers have also demonstrated the potential role of PyMS with ANNs in quantitative biotechnology. Kang et al.106 used the combination to quantify clavulanic-acid production in a Streptomyces clavuligerus fermentation system, while a study by Lee107 indicated that the quantification of clavulanic-acid production by PyMS-ANNs could be used to quantitatively monitor the morphological differentiation process in a Streptomyces fermentation. 

Reading, C. and Cole, M. (1977) Clavulanic acid a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrobial Agents and Chemotherapy, 11, 852—857. 

Ives, P.R. and Bushell, M.E. (1997) Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus. Microbiology (Reading, England), 143, 3573—3579. 

Li, R. and Townsend, C.A. (2006) Rational strain improvement for enhanced clavulanic acid production by genetic engineering of the glycolytic pathway in Streptomyces clavuligerus. Metabolic Engineering, 8, 240-252. 

Aidoo, K.A., Wong, A., Alexander, D.C. et al. (1994) Cloning, sequencing and disruption of a gene from Streptomyces clavuligerus involved in clavulanic acid biosynthesis. Gene, 147, 41—46. 

Jensen, S.E., Elder, K.J., Aidoo, K.A. and Paradkar, A.S., (2000) Enzymes catalyzing the early steps of clavulanic acid biosynthesis are encoded by two sets of paralogous genes in Streptomyces clavuligerus. Antimicrobial Agents and Chemotherapy, 44, 720-726. 

Li, R., Khaleeli, N. and Townsend, C.A. (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. The Journal of Bacteriology, 182, 4087—4095. 

Mycothiol 43 (Scheme 14) is a complex cysteine derivative isolated from Streptomyces clavuligerus, Mycobacterium bovis, and other mycobacteria. It... 

The real breakthrough in identifying a -lactamase inhibitor came in 1976 with the isolation of a bicyclic -lactam, called clavulanic acid la (Fig. 3), produced by a strain of Streptomyces clavuligerus [21,22], In itself, this bicyclic -lactam is a weak antibiotic, but a powerful inhibitor of most class A en-... 

Viet TH, Malla S, Park BC, Liou KY, Lee HC, Sohng JK. (2007) Enhancement of clavulanic acid by replicative and integrative expression of ccaR and cas2 in Streptomyces clavuligerus NRRL 3585. J Microbiol Biotechnol 17 1538-1545. 

Arginine is capable of binding in the active site of PAH but it is not an enzyme substrate. Crystal structures of PAH from Streptomyces clavuligerus show that the metal binding site is very similar to that of arginase and the Mn—Mn distance is 3.3 A The main difference between arginase and PAH is in the binding pocket at the o-amino-terminus of the substrate. ... 

Clavulanic acid is isolated from Streptomyces clavuligerus [60-66], and sulbactam, a sulfone of penicillanic acid, is synthesized from 6-APA [67-69], Both compounds have extremely weak antibacterial properties and act by forming irreversible complexes with beta-lactamase, which inactivates the enzyme, and as a result the beta-lactam antibiotic has time to destroy the microorganism. Currently, a number of combined drugs containing various combinations of beta-lactamase antibiotics and inhibitors are used. 

It progressively inhibits a wide variety of P-lactamases produced by gram positive and negative organisms and is obtained from Streptomyces clavuligerus. It has no antibacterial activity of its own. 

Clavulanic acid is produced by Streptomyces clavuligerus and is structurally related to penicillins. This naturally occurring compound is a specific and irreversible inhibitor of a wide range of bacterial -lactamases and, therefore, can enhance the activity of penicillins and cephalosporins against many resistant organisms. Potassium clavulanate can be administered both orally and perenter-ally in combination with antibiotics sensitive to the action of -lactamases. 

SE Jensen, DWS Westlake, S Wolfe. Production of the pencillin precursor delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) by cell-free extracts from Streptomyces clavuligerus. FEMS Microbiol Lett 49 213-218, 1988. 

JE Baldwin, JW Bird, RA Fields, NM O Callaghan, CJ Schofield. Isolation and partial characterization of ACV synthetase from Cephalosporium acremonium and Streptomyces clavuligerus. J Antibiot 43 1055-1057, 1990. 

J Zhang, AL Demain. Purification of ACV synthetase from Streptomyces clavuligerus. Biotechnol Lett 12 649-654, 1990. 

T Schwecke, Y Aharonowitz, H Palissa, H von Dohren, H Kleinkauf, H van Liempt. Enzymatic characterisation of the multifunctional enzyme 5-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase from Streptomyces clavuligerus. Eur J Biochem 205 687-694, 1992. 

T Schwecke. Untersuchungen zur biosynthese der beta-lactamvorstufe delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valin (ACV) in Streptomyces clavuligerus. Ph D. thesis, Technical University of Berlin, 1992. 

A Khetan, LH Malmberg, DH Sherman, WS Hu. Metabolic engineering of cephalosporin biosynthesis in Streptomyces clavuligerus. Ann NY Acad Sci 782 17-24, 1996. 

SE Jensen, BK Leskiw, LC Vining, Y Aharonowitz, DWS Westlake, S Wolfe. Purification of isopenicillin N synthetase from Streptomyces clavuligerus. Can J Microbiol 32 953-958, 1986. 

---