By Christopher Schofield, Robert Hausinger, C David Garner, Martin J Bollinger, Johanna Myllyharju, Ray Trievel, Tina Muller, Pål Falnes, L Aravind, Robert Sabbatini, Christopher J Schofield, Ronald Wanders, Stefan Martens, Peter Hedden, Inger Andersson, Jan
Because the discovery of the 1st examples of 2-oxoglutarate-dependent oxygenase-catalysed reactions within the Nineteen Sixties, a remarkably large variety of trade reactions and substrates has been published, and large advances were completed in our figuring out of the buildings and catalytic mechanisms. those enzymes are vital agrochemical ambitions and are being pursued as healing goals for a variety of illnesses together with melanoma and anemia.
This ebook offers a significant resource of data that summarizes the most important gains of the basic staff of 2-oxoglutarate-dependent dioxygenases and comparable enzymes. Given the varied contemporary advances and biomedical curiosity within the box, this e-book goals to unite the newest examine for these already operating within the box in addition to to supply an advent for these newly imminent the subject, and for these attracted to translating the elemental technology into medicinal and agricultural benefits.
The booklet starts with 4 vast chapters that spotlight serious elements, together with an summary of attainable catalytic reactions, constructions and mechanisms. the subsequent seventeen chapters specialise in rigorously chosen themes, each one written by way of top specialists within the sector. Readers will locate motives of swiftly evolving learn, from the chemistry of isopenicillin N synthase to the oxidation mechanism of 5-methylcytosine in DNA by way of ten-eleven-translocase oxygenases.
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Extra info for 2-Oxoglutarate-Dependent Oxygenases
J. Schofield, Curr. Opin. Struct. , 2012, 22, 1–10. D. A. Proshlyakov and R. P. Hausinger, in Iron-containing Enzymes: Versatile Catalysts of Hydroxylation Reactions in Nature, ed. D. Kumar and S. P. , 2011, pp. 67–87. P. K. Grzyska, E. H. Appelman, R. P. Hausinger and D. A. Proshlyakov, Proc. Natl. Acad. Sci. , 2010, 107, 3982–3987. R. W. Welford, J. M. Kirkpatrick, L. A. McNeill, M. Puri, N. J. Oldham and C. J. , 2005, 579, 5170–5174. A. G. Prescott and M. D. Lloyd, Nat. Prod. , 2000, 17, 367–383.
15F), followed by dehydration using CurC, decarboxylation via a CurF domain, and mono- or dichloro l-2-aminobutyryl group in cytotrienin synthesis. (D) Trichlorination of leucine by BarB1 and BarB2 to make barbamide. (E) CmaB- or KtzD-dependent hydroxylation of isoleucyl groups for subsequent cyclization to coronamic acids. (F) CurA chlorination of a 3-hydroxy-3-methylglutaryl group as part of curacin A synthesis. (G) KthP halogenation of a piperazyl group during formation of kutznerides. (H) Hydroxylation of a histidyl group during synthesis of bleomycin, tallysomycin and zorbamycin (yellow highlight is a single bond in the case of zorbamycin).
The gene encoding PhnY was identified from a screen of ocean-derived metagenomic DNA that allowed E. coli cells deficient in C–P lyase (Δphn) to grow on 2-aminoethylphosphonic acid as the sole source of phosphorus. 12E)297 much like the reaction of TauD; however, the hydroxylated phosphonate is stable – unlike the hydroxylated sulfonate. 300 Another enzyme participating in the synthesis of dehydrophos by S. 7 2OG-Dependent Oxygenases Involved in Antibiotic Biosynthesis Several 2OG-dependent oxygenases described earlier function in the synthesis of antibiotics, but their actions typically involve provision of small precursor molecules that become incorporated into the final compounds.