Biocatalytic Synthesis of New Cephalosporins Using Immobilized Cephalosporin-Acid Synthetase

IF 1 4区生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Applied Biochemistry and Microbiology Pub Date : 2023-12-14 DOI:10.1134/S0003683823070062

A. V. Sklyarenko, I. A. Groshkova, N. A. Gorbunov, S. V. Yarotsky

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Abstract

Acylation of 1-methyl-5-mercapto-1,2,3,4-tetrazolyl-7-aminocephalosporanic acid, which is the β-lactam nucleus of antibiotics such as Cefamandole, Cefazaflur, Cefotetan, and Cefoperazone, has been carried out using immobilized cephalosporin-acid synthetase as a biocatalyst. Methyl esters of D-mandelic acid, 1(H)-tetrazolylacetic acid, cyanomethylthioacetic acid, thienylacetic acid, D-phenylglycine, and D-p-hydroxyphenylglycine were used as acylating agents. Cefamandole and six chimeric compounds composed of the C3-modified β-lactam nucleus and the acyl parts of various known antibiotics were obtained by the method of kinetically controlled synthesis. Potentially, it is possible to test the antimicrobial activity of the synthesized new chimeric cephalosporins under mild conditions without isolation, directly in the aqueous medium of reaction mixtures after biocatalytic synthesis. The high efficiency of cephalosporin-acid synthetase in the acylation of 1-methyl-5-mercapto-1,2,3,4-tetrazolyl-7-aminocephalosporanic acid with methyl esters of 1(H)-tetrazolylacetic acid and cyanomethylthioacetic acid was demonstrated.

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利用固定化头孢菌素酸合成酶生物催化合成新头孢菌素

以固定化头孢菌素酸合成酶为生物催化剂，对 1-甲基-5-巯基-1,2,3,4-四唑基-7-氨基头孢菌素酸进行了酰化，该酸是头孢孟多、头孢唑呋、头孢替坦和头孢哌酮等抗生素的β-内酰胺核。以 D-扁桃酸、1(H)-四唑基乙酸、氰甲基硫代乙酸、噻吩乙酸、D-苯甘氨酸和 D-对羟基苯甘氨酸的甲酯为酰化剂。通过动力学控制合成的方法，获得了头孢孟多和六种由 C3 改性的 β-内酰胺核和各种已知抗生素的酰基部分组成的嵌合化合物。有可能在温和条件下，不经分离，直接在生物催化合成后反应混合物的水介质中测试合成的新嵌合头孢菌素的抗菌活性。在 1-甲基-5-巯基-1,2,3,4-四唑基-7-氨基头孢烷酸与 1(H)-四唑基乙酸甲酯和氰甲基硫代乙酸甲酯的酰化过程中，头孢菌素酸合成酶的效率很高。

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来源期刊

Applied Biochemistry and Microbiology 生物-生物工程与应用微生物

CiteScore

1.70

自引率

12.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Applied Biochemistry and Microbiology is an international peer reviewed journal that publishes original articles on biochemistry and microbiology that have or may have practical applications. The studies include: enzymes and mechanisms of enzymatic reactions, biosynthesis of low and high molecular physiologically active compounds; the studies of their structure and properties; biogenesis and pathways of their regulation; metabolism of producers of biologically active compounds, biocatalysis in organic synthesis, applied genetics of microorganisms, applied enzymology; protein and metabolic engineering, biochemical bases of phytoimmunity, applied aspects of biochemical and immunochemical analysis; biodegradation of xenobiotics; biosensors; biomedical research (without clinical studies). Along with experimental works, the journal publishes descriptions of novel research techniques and reviews on selected topics.