Contrasting fates for 6-alpha-methylpenicillin N upon oxidation by deacetoxycephalosporin C synthase (DAOCS) and deacetoxy/deacetylcephalosporin C synthase (DAOC/DACS).
6-alpha-methylpenicillin N was synthesised via known routes from 6-aminopenicillanic acid, and tested as a substrate for recombinant DAOCS and DAOC/DACS. Incubation with DAOCS resulted in conversion of 2-oxoglutarate without oxidation of the penicillin substrate ('uncoupled turnover'). Incubation with DAOC/DACS resulted in oxidation to the cephem aldehyde. This is the first example of substrate-induced 'uncoupled turnover', which has been proposed to be an editing mechanism for these enzymes.
Hamilton
C S
CS
The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, South Parks Road, OX1 3QY, Oxford, UK.
Yasuhara
A
A
Baldwin
J E
JE
Lloyd
M D
MD
Rutledge
P J
PJ
D019751:Intramolecular Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
C448500:6-methylpenicillin N; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D011994:Recombinant Proteins; D010105:Oxygenases; C045288:deacetoxycephalosporin C hydroxylase; D019751:Intramolecular Transferases; C038371:deacetoxycephalosporin C synthetase