In industrial penicillin biosynthesis, which specific side-chain precursor must be added to the fermentation medium to obtain penicillin G (benzylpenicillin)?

Introduction / Context:
Penicillin G (also called benzylpenicillin) is a specific penicillin whose side chain is derived from benzyl (phenylmethyl) groups. In industrial microbiology, the side chain of many beta-lactam antibiotics is controlled by feeding a defined precursor to Penicillium chrysogenum during secondary metabolism.

Given Data / Assumptions:

• Desired product: penicillin G (benzylpenicillin).
• Organism: Penicillium chrysogenum under aerobic, fed-batch conditions.
• Side-chain precursors can direct the final penicillin structure.

Concept / Approach:
Penicillin biosynthesis couples the beta-lactam core (6-APA after deacylation) to a side chain supplied either endogenously or exogenously. Supplying phenylacetic acid (PAA) steers acylation toward the benzyl side chain, giving penicillin G. Other nitrogen salts (ammonium sulfate/chloride) support growth but do not specify the side chain. Improper aromatic acids do not yield penicillin G efficiently.

Step-by-Step Solution:

Verification / Alternative check:
Industrial process descriptions consistently list phenylacetic acid or phenoxyacetic acid to direct penicillin G or penicillin V, respectively. This confirms PAA for penicillin G.

Why Other Options Are Wrong:

• Phenyl carbamic acid: not the standard side-chain precursor.
• Ammonium sulfate/chloride: bulk nitrogen sources, not side-chain directors.
• Benzoic acid: does not direct biosynthesis to benzylpenicillin efficiently.

Common Pitfalls:
Confusing growth nutrients with side-chain directing precursors; mixing up penicillin G (PAA) with penicillin V (phenoxyacetic acid).

Final Answer:
Phenylacetic acid (PAA)