High-content nicotinamide synthesis induced by new-feature nitrile hydratase

Abstract

The invention discloses a method of producing nicotinamide through microorganism catalysis. According to a synergistic effect theory, a novel binary composite nitrile hydratase is disclosed, wherein the composite nitrile hydratase is produced through combined cultivation of bacillus pallidus and rhodococcus. The microorganism nitrile hydratase, which is characterized by being high in stereoselectivity, regioselectivity and being resistant to substrates and products in high concentration, is obtained by means of high substrate specificity and thermostability of the bacillus pallidus and a strong promoter effect of the rhodococcus. Meanwhile, by means of introduction of a co-solvent at a certain concentration to the reaction system, the reaction is accelerated. The method is simple and high-efficient, is environment-friendly, can reach not less than 99% in both purity and yield of the product and is suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of microorganisms. In particular, it relates to a method for producing nicotinamide by a novel characteristic nitrile hydratase catalytic method. Background technique [0002] Niacinamide, also known as nicotinamide, belongs to the B group of microorganisms. It is the second largest vitamin among the 14 vitamins in the world. Its current usage is second only to vitamin E. The current annual global usage reaches 60,000 tons. Niacinamide mainly exists in animals, and most of the products used in clinical treatment are synthetic products. Lack of niacinamide will affect the normal respiration and metabolism of cells, resulting in pellagra, stomatitis, glossitis, liver disease and solar dermatitis. Large doses of nicotinamide can reduce the amount of cholesterol and triglycerides. Its physiological effect is similar to that of hydrochloric acid, but it has better water solubility and no obvious vasodilation ef...

AI Technical Summary

Problems solved by technology

The reaction temperature is 90-150°C, the reaction time is 4-8 h, and the maximum conversion rate of 3-cyanopyridine is only 70%.

And it is necessary to separate the unconverted 3-cyanopyridine and ammonia from the product nicotinamide through a multi-step separation process, which is costly and impure; the US patent (USA1133013) also uses chemical methods to catalyze nitriles with manganese dioxide Hydration reaction, the yield of nicotinamide obtained is only 79.28%, and has the disadvantages of high toxicity of raw materials and high amount of catalyst required for the reaction

[0005] Chinese patent (CN1424402A) reports a method for the production of nicotinamide by microbial catalysis, which uses the nitrile hydratase of Corynebacterium propionici to convert 3-cyanopyridine into nicotinamide, avoiding the use of a large amount of chemical catalyst and the reaction There are many steps, but the preparation of enzyme-producing cells is cumbersome; Chinese patent (CN101712944B) reported that 3-cyanopyridine was used as a substrate, Bacillus subtilis was used as a biocatalyst, and the substrate and biocatalyst were coupled and added. Carry out catalytic hydration reaction to obtain nicotinamide, the purity of the obtained nicotinamide is not high, only about 98%