The biosynthesis of avermectins was significantly affected by the nitrogen source used. The maximum yield of AVMs') was achieved in a chemically defined medium with ammonium sulfate as the sole nitrogen source. Higher concentrations of ammonia inhibited the production of AVMs without the inhibition of the growth. AVMs of the group B were prevailing in the complex until I5 mM ammonium sulfate. At higher concentrations, AVMs of the group A predominated. Of various amino acids tested, lysine and asparagine were found to be the best for the biosynthesis of AVMs. The concentration of most amino acids higher than 0.2% inhibited the production, while the mycelium was still growing. The biosynthesis of AVMs was completely suppressed by 15.2 m~ isoleucine, however, this inhibition was reversed by adding alanine at the beginning of cultivation.A considerable attention has recently been devoted to the regulation of biosynthesis of so called secondary metabolites by nitrogen containing substrates. In previous studies, e.g. of the biosynthesis of chlortetracycline, it has already been shown that some amino acids are metabolized to precursors (malonylCoA) forming a nitrogen free. nonaketide skeleton PODOJIL et al. 1973, BEHAL et al. 1979. The regulation of antibiotic biosynthesis by nitrogen compounds was reviewed by AHARONOWITZ (1980). These regulations were studied in producers of p-lactam antibiotics, e.g. Streptomyces clavuligerus (AHARONOWITZ and DEMAIN 1979, B R A~A et al. 1985 In the present work we studied the effect of nitrogen source on the biosynthesis of avermectins. These compounds have neither antibacterial nor antifungal activity, but they are excellent anthelmintics and insecticides. They are pentacyclic lactones with a disaccharide cr-L-oleandrose, which do not contain nitrogen in their molecule, although it is formally possible to derive their starting unit from isoleucine or valine (Fig. 1). Streptomyces avermitilis produces a complex of 8 avermectins consisting of 4 major (Al,, A,=, B1,, B,,) and 4 minor (Albl A,,, B,,, B2d components. As far as their efficiency is concerned Bla is the most interestmg compound.The production of avermectins was studied in a chemically defined medium where amino acids or ammonium sulfate were the only nitrogen source.') AVM = Avermectin

Precursors of monensins (acetate, propionate, butyrate, isobutyrate) affect the total production and the relative proportion of monensins A and B. Addition of propionate into the fermentation medium causes a prevalence of monensin B whereas butyrate and isobutyrate stimulate the production of monensin A and suppress the production of monensin B.

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