Direct enzymatic synthesis of natural penicillins using phenylacetyl-CoA : 6-APA phenylacetyl transferase of Penicillium chrysogenum : Minimal and maximal side chain length requirements.

In vitro synthesis of different natural penicillins (hexanoyl, heptanoyl and octanoyl-penicillin) have been carried out by direct acylation of 6-aminopenicillanic acid (6-APA) with several fatty acid-CoA derivatives (hexanoyl-CoA, heptanoyl-CoA and octanoyl-CoA). The reactions were catalyzed by the enzyme Acyl-CoA: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum AS-P-78. This enzyme only accepts as substrate, aliphatic side chain precursors whose carbon length is between 6 and 8 atoms. Although the enzymatic synthesis of octanoylpenicillin has been previously reported the in vitro synthesis of hexanoyl and heptanoyl penicillins is described here for the first time.