3-lactams biosynthesis

Demain, A.L. and Vaishnav, P. (2006) Involvement of nitrogen-containing compounds in /3-lactam biosynthesis and its control. Critical Reviews in Biotechnology, 26, 67—82. 

Y Aharonowitz, J Bergmeyer, JM Cantoral, G Cohen, AL Demain, U Fink, J King-horn, H Kleinkauf, A MacCabe, H Palissa, E Pfeifer, T Schwecke, H van Liempt, H von Dohren, S Wolfe, J Zhang. 5-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase, the multienzyme integrating the four primary reactions in (3-lactam biosynthesis, as a model peptide synthetase. Bio/Technology 11 807-810, 1993. 

S Kovacevic, MB Tobin, JR Miller. The (3-lactam biosynthesis genes for isopenicillin N epimerase and deacetoxycephalosporin C synthetase are expressed from a single transcript in Streptomyces clavuligerus. J Bacteriol 172 3952-3958, 1990. 

J Kupka, YQ Shen, S Wolfe, AL Demain. Studies on the ring-cyclization and ring-expansion enzymes of (3-lactam biosynthesis in Cephalosporium acremonium. Can J Microbiol 29 488-496, 1983. 

Comparative Genetics and Molecular Biology of 3-Lactam Biosynthesis... 

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... 

Scheme 1 (5-Lactam biosynthesis. Note that the overall process, 2 > 4 includes an...

Brakhage, A. A., Molecular regulation of P-lactam biosynthesis in filamentous fungi. Microbiol. Mol. Biol. Rev., 1998, 62, 547-585. 

A Paradkar, SE Jensen, RH Mosher. Comparative genetics and molecular biology of P-lactam biosynthesis. In WR Strohl, ed. Biotechnology of Antibiotics, 2nd ed. New York Marcel Dekker, 1997, pp 241-277. 

Based on reports of other groups and own experience key parameters were selected, which influence the process performance. Easily-utilized carbon sources such as glucose have been known for long time ago to exert negative effects on -lactam biosynthesis [1-4]. Methionine markedly stimulates CPC and penicillin N (PEN) formation by A. chrysogenum [5, 6] and influences the morphology [7]. 

Kim MG, Lee SB (1996) Penicillin acylase-catalyzed synthesis of P-lactam antibiotics in water-methanol mixtures effect of cosolvent content and chemical nature of substrate on reaction rates and yields. J Mol Catal B Enzym 1 201-211 Kohsaka M, Domain AL (1976) Conversion of penicDlin N to cephalosporin(s) by ceU-free extracts of Cephalosporium acremonium. Biochem Biophys Res Commun 70(2) 465-473 Koreishi M, Tani K, Ise Y et al. (2007) Enzymatic synthesis of P-lactam antibiotics and /V-fatty-acylated amino compounds by the acyl transfer reaction catalyzed by peniciUin V acylase from Streptomyces mobaraensis. Biosci Biotechnol Biochem 71(6) 1582-1586 Kupka JY, Shen, YQ, Wolfe S et al. (1983) Partial purification and properties of the alpha-ketoglutarate-linked ring expansion enzyme of beta-lactam biosynthesis of Cephalosporium acremonium. FEMS Microbiol Lett 16 1-6... 

These two examples illustrate that both precursor flux, in the case of p-lactam biosynthesis, and antibiotic biosynthetic enzyme levels, in the case of tyiosin, can con-... 

Paradkar, A., Jensen, S.E. and Mosher, R.H. (1997) Comparative genetics and molecular biology of -lactam biosynthesis. In Strohl, W.R. (ed.). Biotechnology of Antibiotics. Marcel Dekker, New York, pp. 241-277. 

Kupka, J., Y.-Q. Shen, S. Wolfe, and A. L. Demain Studies on the Ring-Cyclisation and Ring Expanding Enzymes of P-Lactam Biosynthesis in C. acremonium. Can. J. Microbiol. 29, 488 (1983). 

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