Background
Penicillin
The name penicillin is applied to a variety of compounds produced by various species of Penicillium and also to many semi-synthetic penicillins, produced by converting one antibiotic, such as penicillin G, into another, such as ampicillin.
Aspergillus nidulans, another mould fungus, also produces penicillins. The complete biosynthesis pathway for penicillin is extremely complex and unlikely to be achieved in the laboratory.
Commercial production of penicillin
Penicillin G, one of the most active and widely used forms, is manufactured commercially using Penicillium chrysogenum.
The process is carried out in stainless steel fermenters of l0 000 dm3 capacity. The fermenter is steam sterilised and loaded with sterilised growth medium (corn steep liquor) containing lactose, amino acids, mineral salts and other substances.
(Phenylethanoic acid, a metabolic intermediate, is also added, to increase the yield).
An inoculum of strongly growing hyphae is added. Both glucose and nitrate are added periodically. The pH requires adjustment from time to time, to neutralise ammonia produced by the fungus. Temperature is set at first to give the maximum growth rate and then altered to favour penicillin synthesis. The fermenter is continuously stirred and sterile air blown in. An external cooling jacket is used for temperature control. The diagram below shows the type of fermenter used.
Penicillin is a secondary metabolite, produced in large quantities only towards the end of the growth period of the fungus (see the graph below) therefore it is essential for all of the mycelium to reach peak growth at the same time. This is why batch fermentation, rather than a continuous process, is appropriate for penicillin manufacture.
(This may be contrasted with the situation for a primary metabolite, such as alcohol produced by yeast. Production of primary metabolites occurs simultaneously with growth).
After about 160-200 hours, the broth is filtered. Penicillin passes through in the filtrate which is further processed to crystallise the product.
