Phenylacetic acid (PAA) and its derivative, phenylacetate, act as critical side-chain precursors in the industrial fermentation of Penicillin G by the fungus Penicillium chrysogenum. PAA is added to the culture medium, where it is converted into phenylacetyl-CoA and attached to 6-aminopenicillanic acid (6-APA).

Key Aspects of Phenylacetic Acid in Penicillin G Production:

Role as Precursor: PAA is necessary for the biosynthesis of the benzylpenicillin (Penicillin G) side chain.

Industrial Feeding: Because high concentrations of PAA are toxic to P. chrysogenum, it is added in controlled, low amounts to the fermentation medium.

Mechanism: PAA is taken up by the fungus, converted by phenylacetate–CoA ligase (PCL) to phenylacetyl-CoA, and utilized in the final steps of penicillin G synthesis.

Metabolic Pathway: PAA passes through the plasma membrane via passive diffusion of the protonated species.

Other Uses: PAA is also used in the production of drugs like diclofenac, in perfumes, and it is a known precursor for methamphetamine.

Process Details
Optimal Concentrations: Studies indicate that adding PAA at specific concentrations in the growth phase is crucial.

Optimization: Genetic engineering, such as increasing the expression of the phl gene (PAA-CoA ligase), can help the fungus tolerate higher PAA levels and enhance production.

Drawbacks: A portion of the added PAA is oxidized by the fungus, leading to a need for metabolic engineering to rechannel this flux into higher penicillin yields.