کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1375420 | 981938 | 2008 | 4 صفحه PDF | دانلود رایگان |
OxyB catalyzes the first oxidative phenol coupling reaction in vancomycin biosynthesis. OxyB is a P450 hemoprotein whose activity is strictly dependent upon the presence of molecular oxygen. Here, it was shown that label from 18O2 is not incorporated into the monocyclic product during catalysis by OxyB. In addition, it was shown that OxyB can convert a model hexapeptide substrate containing (R)-Tyr6, instead of (S)-Tyr6, covalently linked as a C-terminal thioester to a peptidyl carrier protein (PCP-7S) derived from the vancomycin non-ribosomal peptide synthetase (NRPS), into the corresponding epimeric monocyclic product. The binding of this epimeric hexapeptide-PCP conjugate to the Fe(III) form of OxyB, as monitored by UV–vis spectroscopy, revealed a Kd = 35 ± 5 μM. Thus, the enzyme reveals a surprising lack of stereospecificity in the binding and transformation of these epimeric substrates.
Label from 18O2 is not incorporated into the monocyclic product shown during catalysis by OxyB. Also, a model hexapeptide containing (R)-Tyr6, instead of (S)-Tyr6, is converted by OxyB into the corresponding epimeric monocyclic product.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 10, 15 May 2008, Pages 3081–3084