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One‐Pot Conversion of Cephalosporin C to 7‐Aminocephalosporanic Acid in the Absence of Hydrogen Peroxide
Author(s) -
LopezGallego Fernando,
Batencor Lorena,
Hidalgo Aurelio,
Mateo Cesar,
FernandezLafuente Roberto,
Guisan Jose M.
Publication year - 2005
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200505099
Subject(s) - chemistry , hydrogen peroxide , cephalosporin c , substrate (aquarium) , d amino acid oxidase , hydrolysis , catalase , combinatorial chemistry , yield (engineering) , peroxide , oxidase test , enzyme , organic chemistry , biochemistry , cephalosporin , oceanography , materials science , metallurgy , geology , antibiotics
The main drawback in the production of 7‐aminocephalosporanic acid (7‐ACA) at the industrial level is the inactivation of the enzymes implicated in the process due to the presence of hydrogen peroxide during the reaction. As an alternative, we have developed the conversion of cephalosporin C to 7‐ACA in a single reactor without the presence of hydrogen peroxide during the reaction, achieving more than 80% yield. In order to develop this process, D ‐amino acid oxidase (DAAO) was co‐immobilized with catalase (CAT), which is able to fully eliminate in situ the hydrogen peroxide formed by the neighbouring DAAO molecules. Thus, the product of the reaction is only α‐ketoadipyl‐7‐ACA. This system prevents the inactivation of the oxidase by hydrogen peroxide, solving the main problem of the enzymatic process. Moreover, we have found that α‐ketoadipyl‐7‐ACA is recognized as a substrate by glutaryl acylase (GAC) and hydrolyzed as long as glutaric acid is absent from the reaction medium (because it is able to inhibit the hydrolysis). The low stability of α‐ketoadipyl‐7‐ACA justifies the use of a single reactor, in which glutaryl acylase is already present when this substrate is generated. Thus, the whole process may (and must) be performed in a single step, and in the absence of hydrogen peroxide that could affect the stabilities of the involved enzymes.