Regulation of ACV synthetase: biosynthesis and action

The biosynthesis of cephalosporins has been studied for almost 30 years. Development of cell-free systems began with the later enzymes of the pathway and, in recent years, moved to the early part of the pathway. The first enzyme, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) synthetase was...

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Bibliographic Details
Published inChinese journal of biotechnology Vol. 6; no. 1; p. 1
Main Authors Zhang, J Y, Demain, A L
Format Journal Article
LanguageEnglish
Published United States 1990
Subjects
Acremonium - enzymology
Ammonia - pharmacology
Cephalosporins - biosynthesis
Gene Expression Regulation, Fungal
Glucose - pharmacology
Glucose-6-Phosphate
Glucosephosphates - pharmacology
Glyceric Acids - pharmacology
Peptide Synthases - biosynthesis
Streptomyces - enzymology
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Summary:The biosynthesis of cephalosporins has been studied for almost 30 years. Development of cell-free systems began with the later enzymes of the pathway and, in recent years, moved to the early part of the pathway. The first enzyme, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) synthetase was one of most difficult to demonstrate in cell-free extracts. We recently developed a reproducible system from Cephalosporium acremonium (Banko et al., 1987) and similar activity has been found in Streptomyces clavuligerus (Jensen et al., 1988). With this assay, we have been able to study the regulation of ACV synthetase formation and action. Our results are summarized in this communication. Our comparison of the intracellular specific activities of the beta-lactam synthetases in both C. acremonium c-10 and S. clavuligerus NRRL 3585 indicates that ACV synthetase possesses the lowest activity and appears to be the rate-limiting step in the cephalosporin biosynthetic process. Since it is the initial enzyme in the biosynthetic pathway common to both penicillins and cephalosporins, this makes sense from a cellular economy viewpoint. It is therefore understandable that ACV synthetase would be subject to greater regulatory control than other steps.
ISSN:1042-749X