A-Aminoadipyl-cysteinyl-valine

Although cephalosporin C is divisable into a-aminoadipic acid, cysteine, and valine, the actual mechanism whereby Cephalosporium sp. incorporates the three amino acids into cephalosporin C has not been established, Arnstein and Morris isolated 8 (a-aminoadipyl) cysteinyl valine from mycelia of Penicillium chrysogenum and suggested that the tripeptide is a precursor in all penicillin biosynthesis.. This same tripeptide also appears to be found in the intracellular pool of Cephalosporium sp.- The final postulated step in the biosynthesis of penicillin is an acyl transfer reaction, or the production of 6-aminopeni-cillanic acid if precursor is not added. Cephalosporium sp. apparently do not produce sidechain amidases or acyl transferases, and no 7-ACA has been reported found in the fermentation. Thus, to obtain clinically useful antibiotics, chemical manipulation of cephalosporin C is necessary. Synthesis of many 7-acyl derivatives was possible once a practical cleavage reaction made available large amounts of 7-ACA from cephalosporin C. of these derivatives, sodium cephalothin was the first... 

Bauer, K. Zur Biosynthese der Penicilline Bildung von 5-(a-Aminoadipyl)cysteinyl-valin in Extracten von Penicillium chrysogenum. Z. Naturforsch. B, 25, 1125 (1970). 

Neuss, N., D. M. Berry, J. Kupka, A. L. Demain, S. W. Queener, D. C. Duckworth, and L. L. Huckstep High Performance Liquid Chromatography (HPLC) of Natural Products V The Use of HPLC in the Cell-Free Biosynthetic Conversion of a-Aminoadipyl-cysteinyl-valine (LLD) into Isopenicillin N. J. Antibiotics 35, 580 (1982). 

ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTHEPE] (Vol 3) d-(L-a-Aminoadipyl)-L-cysteinyl-D-valine (LLD-ACV) [32467-88-2]... 

The (5-lactam antibiotics are now so extensively described that we cannot attempt to summarize the literature. Since our emphasis is on sulfur, we note that the sulfur atoms of the thiazolidine or dihydrothiazine rings derive from a common tripeptide, 8-(L-a-aminoadipyl)-L-cysteinyl-D-valine 1, ACV or Arnstein tripeptide . ACV is converted to a (5-lactam structure, isopenicillin N 2 and thereafter, the two pathways diverge, i.e. to benzylpenicillin 3 or to cephalosporin C 4 (Scheme 1). There have been extensive studies of the genes and enzymes involved in (5-lactam biosynthesis.18,19... 

Kennedy J, Turner G. (1996) 5-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase is a rate limiting enzyme for penicillin production in Aspergillus nidulans. Mol Gen Genet 253 189-197. 

A simple example is the tripeptide precursor of the penicillin antibiotics, called ACV, an abbreviation for S-(L-a-aminoadipyl)-L-cysteinyl-D-valine. The amino acid precursors for ACV are L-a-aminoadipic acid (an unusual amino acid derived by modification of L-lysine), L-cysteine, and L-valine (not o-valine). 

The tripeptide precursor is called ACV, an abbreviation for 8-(L-a-aminoadipyl)-L-cysteinyl-D-valine. ACV is an acronym, and does not refer to the systematic abbreviations for amino acids described in Table 13.1. ACV is the linear tripeptide that leads to isopenicillin N, the first intermediate with the fused-ring system found in the penicillins. 

L-a-Aminoadipyl)-L-Cysteinyl-D-Valine Synthetase as a Model Tripeptide Synthetase... 

MA Tavanlar. Molecular characterisation of the 8-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) from filamentous fungi determination of the domain arrangement, cloning and expression of the third domain. Ph.D. thesis, University of Los Banos/Technical University of Berlin, 1996. 

RM Adlington, JE Baldwin, M Lopez-Nieto, JA Murphy, N Patel. A study of the biosynthesis of the tripeptide 5-(L-a-aminoadipyl)-L-cysteinyl-D-valine in a (3-lactam-negative mutant of Cephalosporium acremonium. Biochem J 213 573-576, 1983. 

G Banko, AL Demain, S Wolfe. 8-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACV synthetase) a multifunctional enzyme with broad substrate specificity for the synthesis of penicillin and cephalosporin precursors. J Am Chem Soc 109 2858-2860, 1987. 

SE Jensen, DWS Westlake, S Wolfe. Production of the penicillin precursor 5-(L-a-aminoadipyl)-L-cysteinyl-D-valine (ACV) by cell-free extracts from Streptomyces clavuligerus. FEMS Microbiol Lett 49 213-218, 1988. 

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