Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) (ACVS)

Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) is a large, multifunctional enzyme that catalyzes the first committed step in the biosynthesis of beta-lactam antibiotics, such as penicillin and cephalosporin (UniProt P16271). It belongs to the family of non-ribosomal peptide synthetases (NRPS) and functions by condensing three precursor amino acids—L-alpha-aminoadipic acid, L-cysteine, and L-valine—into the tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (PubMed: 1901435). This complex reaction involves multiple catalytic domains, including adenylation, peptidyl carrier protein (thiolation), and condensation domains, as well as an epimerization domain that converts L-valine to the D-isomer (Wikipedia: ACV synthetase). While ACVS is primarily found in filamentous fungi like Penicillium chrysogenum and certain bacteria like Streptomyces clavuligerus, it is not present in humans, making it a potential target for novel antimicrobial strategies (PubMed: 2254431). In the pharmaceutical industry, ACVS is a major focus for metabolic engineering and synthetic biology to improve the yield of antibiotic production or to generate novel peptide derivatives (NCBI: PMC3823110). Although there are currently no FDA-approved drugs that target ACVS, research into NRPS inhibitors continues as a pathway toward addressing antibiotic resistance (PubMed: 25614563).

Other names

ACV synthetaseACV synthaseL-alpha-aminoadipyl-L-cysteinyl-D-valine synthetasedelta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthase

Inhibition of the non-ribosomal peptide synthesis of the ACV tripeptide precursor, which is the essential first step in the production of beta-lactam antibiotics.