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dc.contributor.author David H. en_US
dc.contributor.author David C. en_US
dc.contributor.author Larissa M. en_US
dc.contributor.author Horacio en_US
dc.contributor.author Michael R. en_US
dc.contributor.author Youngchang en_US
dc.contributor.author Steven L. en_US
dc.contributor.author Miharu en_US
dc.date.accessioned 2009-09-09T08:38:42Z
dc.date.available 2009-09-09T08:38:42Z
dc.date.issued 2004 en_US
dc.identifier http://dx.doi.org/10.1110/ps.03384804 en_US
dc.identifier.citation Sherman , D H , Lamb , D C , Podust , L M , Bach , H , Waterman , M R , Kim , Y , Kelly , S L & Arase , M 2004 , ' Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways ' Science , pp. 255-268 . , 10.1110/ps.03384804 en_US
dc.identifier.other PURE: 123903 en_US
dc.identifier.other dspace: 2160/3018 en_US
dc.identifier.uri http://hdl.handle.net/2160/3018
dc.description.abstract The genus Streptomyces produces two-thirds of microbially derived antibiotics. Polyketides form the largest and most diverse group of these natural products. Antibiotic diversity of polyketides is generated during their biosynthesis by several means, including postpolyketide modification performed by oxidoreductases, a broad group of enzymes including cytochrome P450 monooxygenases (CYPs). CYPs catalyze site-specific oxidation of macrolide antibiotic precursors significantly affecting antibiotic activity. Efficient manipulation of Streptomyces CYPs in generating new antibiotics will require identification and/or engineering of monooxygenases with activities toward a diverse array of chemical substrates. To begin to link structure to function of CYPs involved in secondary metabolic pathways of industrially important species, we determined the X-ray structure of Streptomyces coelicolor A3(2) CYP154A1 at 1.85 Å and analyzed it in the context of the closely related CYP154C1 and more distant CYPs from polyketide synthase (EryF) and nonribosomal peptide synthetase (OxyB) biosynthetic pathways. In contrast to CYP154C1, CYP154A1 reveals an active site inaccessible from the molecular surface, and an absence of catalytic activities observed for CYP154C1. Systematic variations in the amino acid patterns and length of the surface HI loop correlate with degree of rotation of the F and G helices relative to the active site in CYP154A1-related CYPs, presumably regulating the degree of active site accessibility and its dimensions. Heme in CYP154A1 is in a 180° flipped orientation compared with most other structurally determined CYPs. en_US
dc.format.extent 14 en_US
dc.relation.ispartof Science en_US
dc.title Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways en_US
dc.contributor.pbl Aberystwyth University en_US
dc.contributor.pbl Institute of Biological, Environmental and Rural Sciences en_US


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