THE MULTIFUNCTIONAL PEPTIDE SYNTHETASE PERFORMING THE 1ST STEP OF PENICILLIN BIOSYNTHESIS IN PENICILLIUM-CHRYSOGENUM IS A 421-073 DALTON PROTEIN SIMILAR TO BACILLUS-BREVIS PEPTIDE ANTIBIOTIC SYNTHETASES

The nucleotide sequence of the Penicillium chrysogenum Oli13 acvA gene encoding δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase, which performs the first step in penicillin biosynthesis, has been determined. The acvA gene contains an open reading frame of 11238 bp encoding a protein of 3746 amino acids with a predicted mol. wt of 421073 dalton. Three domains within the protein of ~570 amino acids have between 38% and 43% identity with each other and share similarity with two antibiotic peptide synthetases from Bacillus brevis as well as two other enzymes capable of performing ATP-pyrophosphate exchange reactions. The acvA gene is located close to the pcbC gene encoding isopenicillin N synthetase, the enzyme for the second step of β-lactam biosynthesis, and is transcribed in the opposite orientation to it. The intergenic region of 1107 bp from which the acvA and pcbC genes are divergently transcribed has also been sequenced.