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Transformation of structurally diverse steroidal analogues by the fungus Corynespora cassiicola CBS 161.60 results in generation of 8β-monohydroxylated metabolites with evidence in favour of 8β-hydroxylation through inverted binding in the 9α-hydroxylase
- Source :
- Biochimica et biophysica acta. 1811(12)
- Publication Year :
- 2011
-
Abstract
- Corynespora cassiicola has a unique but unexplored ability amongst fungi, in that it can hydroxylate 17α-hydroxyprogesterone at the highly hindered C-8 position of the steroid nucleus. In order to gain greater understanding of the mechanistic basis and capability of the 8β-hydroxylase we have transformed a range of structurally diverse androgens and progestogens with this organism. This has revealed that both steroid types can be hydroxylated at the 8β-position. The collective data has demonstrated the first time that 8β-hydroxylation occurs through inverted binding within a 9α-hydroxylase of the fungus. In the case of the progestogens, for this to occur, the presence of 17α-oxygen functionality (alcohol or epoxide) was essential. Remarkably monohydroxylation of 17α-hydroxyprogesterone at carbons 8β and 15β has strongly indicated that the responsible hydroxylase has 2 different binding sites for the ring-A ketone. Unusually, with one exception, all hydroxylation occurred at axial protons and in the case of the progestogens, all above the plane of the ring system. In general all maximally oxidised metabolites contained four oxygen atoms. The importance of these findings in relation to 8β-hydroxylation of these steroids is discussed.
- Subjects :
- Ketone
Magnetic Resonance Spectroscopy
Stereochemistry
medicine.medical_treatment
Cell Culture Techniques
Epoxide
Plasma protein binding
Crystallography, X-Ray
Hydroxylation
Steroid
chemistry.chemical_compound
Industrial Microbiology
Ascomycota
medicine
Binding site
Corynespora cassiicola
Molecular Biology
Biotransformation
chemistry.chemical_classification
Binding Sites
Progestogen
biology
Molecular Structure
Cell Biology
biology.organism_classification
chemistry
Biochemistry
Steroid Hydroxylases
Androgens
Steroids
Progestins
Oxidation-Reduction
Protein Binding
Subjects
Details
- ISSN :
- 00063002
- Volume :
- 1811
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta
- Accession number :
- edsair.doi.dedup.....74cd0f6d97d50f7392d69d864d380b45