A new esterase for the cleavage of pivalic acid-containing prodrug esters of cephalosporins.
An extracellular esterase from the actinomycetes Amycolatopsis orientalis was found by screening. It is capable of splitting the isomeric mixture (K/J) of (I, Scheme 1) into 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid, pivalic acid, and acetaldehyde with a high yield. The purified enzyme of 55.4 Kd by SDS-PAGE shows an N-terminal sequence of VRTCADLVRTYDLPGAVTH. The isoelectric point is 8.9 +/- 0.1. It can be immobilized with good yield to VA-Epoxy Biosynth. Besides the above-mentioned reaction, the esterase cleaves many other esters such as methyl-2-chloropropionic acid.
Sauber
K
K
Hoechst AG, Pharma Research, Frankfurt, Germany.
Aretz
W
W
Meiwes
J
J
Wollmann
T
T
D039903:Actinobacteria / Q000201:enzymology; D000595:Amino Acid Sequence; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000378:metabolism; D004950:Esterases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D004952:Esters; D005285:Fermentation; D007700:Kinetics; D008969:Molecular Sequence Data; D010421:Pentanoic Acids; D010446:Peptide Fragments / Q000737:chemistry; D011355:Prodrugs; D013379:Substrate Specificity
D002511:Cephalosporins; D004952:Esters; D010421:Pentanoic Acids; D010446:Peptide Fragments; D011355:Prodrugs; C005566:pivalic acid; D004950:Esterases