The Influence of Chemical Mutagenesis on the Properties of the Cyclosporine a High-Producer Strain Tolypocladium inflatum VKM F-3630D

Abstract

The effects of treatment with the chemical mutagen N-nitroso-N-methylurea (NMU) on the survival rate, morphological variability, and the level of production of cyclosporine A (CyA) in the Tolypocladium inflatum subsporum blastosporum strain VKM F-3630D were studied. The range of exposure to the dose of the mutagen (incubation time and concentration of HMU) was determined. The lethal and sublethal doses, as well as the conditions under which the highest variability in the levels of CyA production was observed, were determined. It was shown that the most efficient method to further increase CyA production in the studied high-producer T. inflatum strain is mutagenic treatment with 0.1% HMU for 2 h. In this case, we observed a relatively high level of survival of clones (80–85%), a low level of their morphological variability (10–15%), and a wide range in the CyA production level (80–170%) as compared to the original strain. This enabled us to select a number of clones with an increased CyA production level. The yield of the target metabolite was maximal in clone no. 13-27, where the CyA production level increased by 1.6–1.7 times.