Enhanced Enzymatic Synthesis of a Cephalosporin, Cefadroclor, in the Presence of Organic Co-solvents.
In this study, we investigated the enzymatic synthesis of a semi-synthetic cephalosporin, cefadroclor, from 7-aminodesacetoxymethyl-3-chlorocephalosporanic acid (7-ACCA) and p-OH-phenylglycine methyl ester (D-HPGM) using immobilized penicillin G acylase (IPA) in organic co-solvents. Ethylene glycol (EG) was employed as a component of the reaction mixture to improve the yield of cefadroclor. EG was found to increase the yield of cefadroclor by 15-45%. An investigation of altered reaction parameters including type and concentration of organic solvents, pH of reaction media, reaction temperature, molar ratio of substrates, enzyme loading, and IPA recycling was carried out in the buffer mixture. The best result was a 76.5% conversion of 7-ACCA, which was obtained from the reaction containing 20% EG (v/v), D-HPGM to 7-ACCA molar ratio of 4:1 and pH 6.2, catalyzed by 16 IU mL-1IPA at 20 °C for 10 h. Under the optimum conditions, no significant loss of IPA activity was found after seven repeated reaction cycles. In addition, cefadroclor exhibited strong inhibitory activity against yeast, Bacillus subtilis NX-2, and Escherichia coli and weaker activity against Staphylococcus aureus and Pseudomonas aeruginosa. Cefadroclor is a potential antibiotic with activity against common pathogenic microorganisms.
State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.|College of Food Science and Light Industry, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.
Kun
K
Liu
State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.|College of Food Science and Light Industry, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.
Sha
S
Li
State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.|College of Food Science and Light Industry, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.
Xiao
X
Pang
State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.|College of Food Science and Light Industry, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China.
Zheng
Z
Xu
School of Life Science, Huaiyin Normal University, No. 111 West of Changjiang Road, Huaiyin District, 223300, Huai'an, China. dcli@hytc.edu.cn.
Dengchao
D
Li
State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China. xuh@njtech.edu.cn.|College of Food Science and Light Industry, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China. xuh@njtech.edu.cn.
Hong
H
Xu
D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000254:growth & development; D002511:Cephalosporins / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D004800:Enzymes, Immobilized / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D019855:Ethylene Glycol / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D010399:Penicillin Amidase / Q000737:chemistry / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D012997:Solvents / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013696:Temperature
D000890:Anti-Infective Agents; D002511:Cephalosporins; D004800:Enzymes, Immobilized; D012997:Solvents; C033393:methyl phenylglycine; D010399:Penicillin Amidase; D019855:Ethylene Glycol; D005998:Glycine
Antimicrobial activity; Cephalosporin; Enzymatic synthesis; Organic co-solvents; Penicillin G acylase