Penicillin is a secondary metabolite of fungus ''Penicillium'' that is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin.
- α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-Lysine + β-lactam
The by-product L-Lysine inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production.
The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress and will produce plenty of penicillin. The carbon sources that are available are also important: Glucose inhibits penicillin, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must be controlled automatically.
Penicillin production emerged as an industry as a direct result of World War II. During the war, there was an abundance of jobs available in the U.S. on the home front. The War Production Board was founded to monitor job distribution and production. Penicillin was produced in huge quantities during the war and the industry prospered.
In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe. At the time of this plan, 425 million units per year were being produced. As a direct result of the war and the War Production Board, by June 1945 over 646 billion units per year were being produced.
In recent years, the biotechnology method of directed evolution has been applied to produce by mutation a large number of Penicillium strains. These directed-evolution techniques include error-prone PCR, DNA shuffling, ITCHY, and strand overlap PCR.
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