Hamilton C S, Yasuhara A, Baldwin J E, Lloyd M D, Rutledge P J
The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, South Parks Road, OX1 3QY, Oxford, UK.
Bioorg Med Chem Lett. 2001 Sep 17;11(18):2511-4. doi: 10.1016/s0960-894x(01)00470-x.
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.
6-α-甲基青霉素N通过已知路线由6-氨基青霉烷酸合成,并作为重组DAOCS和DAOC/DACS的底物进行测试。与DAOCS一起孵育导致2-氧代戊二酸的转化,而青霉素底物未被氧化(“解偶联周转”)。与DAOC/DACS一起孵育导致氧化为头孢烯醛。这是底物诱导的“解偶联周转”的第一个例子,有人提出这是这些酶的一种编辑机制。