Back to Search
Start Over
Molecular determinants for selective C25-hydroxylation of vitamins D2 and D3 by fungal peroxygenases
- Source :
- UPCommons. Portal del coneixement obert de la UPC, Universitat Politècnica de Catalunya (UPC), Recercat. Dipósit de la Recerca de Catalunya, instname, Digital.CSIC. Repositorio Institucional del CSIC
- Publication Year :
- 2016
- Publisher :
- Royal Society of Chemistry (UK), 2016.
-
Abstract
- 8 páginas.-- 7 figuras.-- 45 referencias.-- Electronic supplementary information (ESI) available: Molecular model for Ccinerea peroxygenase obtained using A. aegerita's crystal structure as the template. See DOI: 10.1039/c5cy00427f<br />Hydroxylation of vitamin D by Agrocybe aegerita and Coprinopsis cinerea peroxygenases was investigated in a combined experimental and computational study. 25-Monohydroxylated vitamins D3 (cholecalciferol) and D2 (ergocalciferol), compounds of high interest in human health and animal feeding, can be obtained through a reaction with both fungal enzymes. Differences in conversion rates, and especially in site selectivity, were observed. To rationalize the results, diffusion of D2 and D3 on the molecular structure of the two enzymes was performed using the PELE software. In good agreement with experimental conversion yields, simulations indicate more favorable energy profiles for the substrates' entrance in C. cinerea than for A. aegerita enzyme. On the other hand, GC-MS analyses show that while a full regioselective conversion of D2 and D3 into the active C25 form is catalyzed by C. cinerea peroxygenase, A. aegerita yielded a mixture of the hydroxylated D3 products. From the molecular simulations, relative distance distributions between the haem compound I oxygen atom and H24/H25 atoms (hydrogens on C24 and C25, respectively) were plotted. Results show large populations for O–H25 distances below 3 Å for D2 and D3 in C. cinerea in accordance with the high reactivity observed for this enzyme. In A. aegerita, however, cholecalciferol has similar populations (below 3 Å) for O–H25 and O–H24, which can justify the hydroxylation observed in C24. In the case of ergocalciferol, due to the bulky methyl group in position C24, very few structures are found with O–H24 distances below 3 Å and thus, as expected, the reaction was only observed at the C25 position.<br />This work was supported by the INDOX (KBBE-2013-7-613549) and PELE (ERC-2009-Adg 25027) EU projects, and by the BIO2011-26694 and CTQ2013-48287 projects of the Spanish Ministry of Economy and Competitiveness.
- Subjects :
- 0301 basic medicine
Vitamines
Stereochemistry
A. aegerita
Vitamins Computational studies
Hydroxylation
Molecular determinants
Catalysis
Experimental conversion
03 medical and health sciences
chemistry.chemical_compound
Coprinopsis cinerea
medicine
Regioselective conversion
Reactivity (chemistry)
Molècules
Relative distances
Site selectivity
chemistry.chemical_classification
biology
Agrocybe
Enginyeria mecànica::Impacte ambiental [Àrees temàtiques de la UPC]
Oxygenations of aliphatic
Vitamins
Molecules
biology.organism_classification
3. Good health
Ergocalciferol
Molecular oxygen
030104 developmental biology
Enzyme
chemistry
Molecular simulations
Cholecalciferol
Molecular structure
Methyl group
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- UPCommons. Portal del coneixement obert de la UPC, Universitat Politècnica de Catalunya (UPC), Recercat. Dipósit de la Recerca de Catalunya, instname, Digital.CSIC. Repositorio Institucional del CSIC
- Accession number :
- edsair.doi.dedup.....ce5c6edbc870c124cdc65d5184aaa062