Antibiotics are generally produced as a result of some environmental stress that triggers a metabolic response. The biosynthesis
of β-lactam antibiotics is strongly influenced by environmental factors such as carbon source, nitrogen source, phosphates and levels of same in the fermentation medium used to grow the producer microorganism. Different nitrogen sources used are Soya meal, nitrates, ammonium salts, amino acids, and mineral salts. The β-lactam antibiotics are synthesized by a range of microorganisms. The process involved in their production is influenced by the type of nitrogen source used. Ammonium ions, except at very low concentrations, exert negative effects via nitrogen metabolite repression, sometimes involving the nitrogen regulatory gene nre. Certain
amino acids are precursors or inducers, whereas others are involved in repression and, in certain cases, as inhibitors of biosynthetic enzymes and of enzymes supplying precursors. The most important amino acids from the viewpoint of regulation are lysine, methionine, glutamate and valine. Lysine exerts a negative influence on β-lactam synthesis through feedback inhibition or at times feedback repression in fungi. However it stimulates cephalosporin production in
Actinomycetes. Methionine has a positive effect on
Penicillin N and cephalosporin production in A.chrysogenum and A. nidulans. β-lactam Glutamate induces penicillin formation in P.chrysogenum and its intracellular concentration rises just before penicillin production begins. Valine is required in high amounts as a precursor for penicillin and cephalosporin production. Surprisingly, diamines such as diaminopropane, putrescine and cadaverine induce cephamycin production by actinomycetes. In addition to penicillins and cephalosporins made by fungi and cephamycins made by actinomycetes, other ß-lactams are made by actinomycetes and unicellular bacteria. These include clavams (e.g., Clavulanic acid), carbapenems (e.g., thienamycin), nocardicins and monobactams. Here also, amino acids are precursors and inhibitors, but only little is known about regulation. In the case of the simplest carbapenem made by unicellular bacteria, i.e., 1-carba-2-em-3-carboxylic acid, quorum sensors containing homoserine lactone are inducers.