The majority of characterized cytochrome P450 enzymes in actinomycete secondary metabolic pathways are strictly substrate-, regio-, and stereo-specific. Examples of multifunctional biosynthetic cytochromes P450 with broader substrate and regio-specificity are growing in number and are of particular interest for biosynthetic and chemoenzymatic applications. MycG is among the first P450 monooxygenases characterized that catalyzes both hydroxylation and epoxidation reactions in the final biosynthetic steps, leading to oxidative tailoring of the 16-membered ring macrolide antibiotic mycinamicin II in the actinomycete Micromonospora griseorubida. The ordering of steps to complete the biosynthetic process involves a complex substrate recognition pattern by the enzyme and interplay between three tailoring modifications as follows: glycosylation, methylation, and oxidation. To understand the catalytic properties of MycG, we structurally characterized the ligand-free enzyme and its complexes with three native metabolites. These include substrates mycinamicin IV and V and their biosynthetic precursor mycinamicin III, which carries the monomethoxy sugar javose instead of the dimethoxylated sugar mycinose. The two methoxy groups of mycinose serve as sensors that mediate initial recognition to discriminate between closely related substrates in the post-polyketide oxidative tailoring of mycinamicin metabolites. Because x-ray structures alone did not explain the mechanisms of macrolide hydroxylation and epoxidation, paramagnetic NMR relaxation measurements were conducted. Molecular modeling based on these data indicates that in solution substrate may penetrate the active site sufficiently to place the abstracted hydrogen atom of mycinamicin IV within 6 Å of the heme iron and ~4 Å of the oxygen of iron-ligated water.
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http://dx.doi.org/10.1074/jbc.M112.410340 | DOI Listing |
J Biol Chem
December 2024
Structural Biochemistry, Department of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany. Electronic address:
Two-component flavin-dependent monooxygenases are of great interest as biocatalysts for the production of pharmaceuticals and other relevant molecules, as they catalyze chemically important reactions such as hydroxylation, epoxidation and halogenation. The monooxygenase components require a separate flavin reductase, which provides the necessary reduced flavin cofactor. The tryptophan halogenase Thal from Streptomyces albogriseolus is a well-characterized two-component flavin-dependent halogenase.
View Article and Find Full Text PDFChemistry
December 2024
Okayama University: Okayama Daigaku, Research Institute for Interdisciplinary Science, JAPAN.
Grafting carbon-based nanomaterials (CNMs) with polyglycerol (PG) improves their application potentials in biomedicine and electronics. Although "grafting from" method offers advantages over "grafting to" one in terms of operability and versatility, little is known about the reaction process of glycidol with the surface groups onto CNMs. By using graphene oxide (GO) as a multi-functional model material, we examined the reactivity of the surface groups on GO toward glycidol molecules via a set of model reactions.
View Article and Find Full Text PDFActa Crystallogr E Crystallogr Commun
October 2024
Cryssmat-Lab, Cátedra de Física, DETEMA, Facultad de Química, Universidad de la República, Av. General Flores 2124, CP 11800, Montevideo, Uruguay.
J Am Chem Soc
December 2024
Polymer Synthesis Laboratory, Laboratory, Chemistry Program, KAUST Catalysis Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia.
Uniform sugar-functionalized polyesters combine the benefits of sugar's structural diversity, biocompatibility, and biodegradability with precise postfunctionalization capabilities, making them a highly valuable class of materials with extensive application potential. However, the irregular placement of hydroxyl groups has limited the synthesis of these polyesters. Here, we present the first platform for uniform sugar-functionalized polyesters via regioselective ring-opening copolymerizations (ROCOPs) of allopyranoside anhydrosugar epoxide (, derived from d-glucose) with cyclic anhydrides, followed by complete selective deprotection.
View Article and Find Full Text PDFACS Omega
December 2024
Industrial Efficient Utilization of Domestic Cigar Tobacco Key Laboratory of Sichuan Province, Shifang 618499, China.
Sustainable poly(lactic acid) (PLA)/poly(propylene carbonate) (PPC) blends were compatibilized by the environmentally friendly epoxidized soybean oil (ESO) through the chemical reaction of epoxy functional groups on ESO with the terminated carboxyl and hydroxyl groups of PLA/PPC. The compatibilization effect of ESO was confirmed by Fourier transform infrared spectroscopy, rheological property testing, differential scanning calorimetry, and morphological observations. It was revealed that the molecular chain entanglement between PLA and PPC was significantly enhanced and the dispersed PPC phase size was decreased, which endowed the blend with high viscosity modulus, low tan δ, and great stretchability, especially for the blend containing 1.
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