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Anaerobic biosynthesis of 1-butanol from glucose is investigated in recombinant Escherichia coli strains which form butyryl-CoA using the heterologous enzyme complex of clostridia or as a result of a reversal in the action of native enzymes of the fatty acid beta-oxidation pathway. It was revealed that when the basic pathways of acetic and lactic acid formation are inactivated due to deletions in the ackA, pta, poxB, and ldhA genes, the efficiency of butyryl-CoA biosynthesis and its reduced product, i.e., 1-butanol, by two types of recombinant stains is comparable. The limiting factor for 1-butanol production by the obtained strains is the low substrate specificity of the basic CoA-dependent alcohol/aldehyde AdhE dehydrogenase from E. coli to butyryl-CoA. It was concluded that, in order to construct an efficient 1-butanol producer based on a model strain synthesizing butyryl-CoA as a result of a reversal in fatty acid beta-oxidation enzymes, it is necessary to provide intensive formation of acetyl-CoA and enhanced activity of alternative alcohol and aldehyde dehydrogenases in the cells of a strain.

Enteral and inhaled n-butanol given to albino rats was tested for toxicity in 2 series of subacute 30-day toxicological experiments. Enteral and inhalant administration caused membrano-, hepato-, adrenotoxic effects, and inhalant administration produced neurotoxic ones. The threshold dose was 0.2 mg/kg, the maximum ineffective one was 0.04 mg/kg. The threshold concentration was not established in the experiment. The less than 95% confidence limits of reference points (BMDL and BMCL), which cause a 10%-increase in the frequency of adverse reactions (blood catalase induction), were 0.052 mg/kg with enteral administration and 0.18 mg/m3 (0.076 mg/kg) on inhalation. The comparative toxicity coefficient (BMDLent/BMDLinh = 0.68) for n-butanol suggests that there is no difference in toxicity on different routes of administration.