604-19-3

Usage

Uses

6β-Hydroxy Progesterone is a metabolite of Progesterone (P755900).

Definition

ChEBI: A 3-oxo-Delta4-steroid that is progesterone in which the hydrogen at the 6beta-position is substituted by a hydroxy group.

InChI:InChI=1/C21H30O3/c1-12(22)15-4-5-16-14-11-19(24)18-10-13(23)6-8-21(18,3)17(14)7-9-20(15,16)2/h10,14-17,19,24H,4-9,11H2,1-3H3/t14-,15+,16-,17-,19+,20+,21+/m0/s1

Upstream product

• 104948-25-6 3-O-benzylpregnenolone 
• 57-83-0 Progesterone 

Relevant academic research and scientific papers

Engineering of CYP106A2 for steroid 9α- and 6β-hydroxylation

CYP 106A2 from Bacillus megaterium ATCC 13368 has been described as a 15β-hydroxylase showing also minor 11α-, 9α- and 6β-hydroxylase activity for progesterone conversion. Previously, mutant proteins with a changed selectivity towards 11α-OH-progesterone have already been produced. The challenge of this work was to create mutant proteins with a higher regioselectivity towards hydroxylation at positions 9 and 6 of the steroid molecule. 9α-hydroxyprogesterone exhibits pharmaceutical importance, because it is a useful intermediate in the production of physiologically active substances which possess progestational activity. Sixteen mutant proteins were selected from a library containing mutated proteins created by a combination of site-directed and saturation mutagenesis of active site residues. Four mutant proteins out of these catalyzed the conversion of progesterone to 9α-OH-progesterone as a main product. For further optimization site-directed mutagenesis was performed. The introduction of seven mutations (D217V, A243V, A106T, F165L, T89N, T247V or T247W) into these four mutant proteins led to 28 new variants, which were also used for an in vivo conversion of progesterone. The best mutant protein, F165L/A395E/G397V, showed a ten-fold increase in the selectivity towards progesterone 9α-hydroxylation compared with the wild type CYP106A2. Also 6β-OH-progesterone is a pharmaceutically important compound, especially as intermediate for the production of drugs against breast cancer. For the rational design of mutant proteins with 6β-selectivity, docking of the 3D-structure of CYP106A2 with progesterone was performed. The introduction of three mutations (T247A, A243S, F173A) led to seven new mutant proteins. Clone A243S showed the greatest improvement in 6β-selectivity being more than ten-fold. Finally, an in vivo conversion of 11-deoxycorticosterone (DOC), testosterone and cortisol with the best five mutant proteins displaying 9α- or 6β-hydroxylation, respectively, of progesterone was performed to investigate whether the introduced mutations also effected the conversion of other substrates.

Double site saturation mutagenesis of the human cytochrome P450 2D6 results in regioselective steroid hydroxylation

The human cytochrome P450 2D6 (CYP2D6) is one of the major human drug metabolizing enzymes and acts preferably on substrates containing a basic nitrogen atom. Testosterone - just as other steroids - is an atypical substrate and only poorly metabolized by CYP2D6. The present study intended to investigate the influence of the two active site residues 216 and 483 on the capability of CYP2D6 to hydroxylate steroids such as for example testosterone. All 400 possible combinatorial mutations at these two positions have been generated and expressed individually in Pichia pastoris. Employing whole-cell biotransformations coupled with HPLC-MS analysis the testosterone hydroxylase activity and regioselectivity of every single CYP2D6 variant was determined. Covering the whole sequence space, CYP2D6 variants with improved activity and so far unknown regio-preference in testosterone hydroxylation were identified. Most intriguingly and in contrast to previous literature reports about mutein F483I, the mutation F483G led to preferred hydroxylation at the 2β-position, while the slow formation of 6β-hydroxytestosterone, the main product of wild-type CYP2D6, was further reduced. Two point mutations have already been sufficient to convert CYP2D6 into a steroid hydroxylase with the highest ever reported testosterone hydroxylation rate for this enzyme, which is of the same order of magnitude as for the conversion of the standard substrate bufuralol by wild-type CYP2D6. Furthermore, this study is also an example for efficient human CYP engineering in P. pastoris for biocatalytic applications and to study so far unknown pharmacokinetic effects of individual and combined mutations in these key enzymes of the human drug metabolism. 400 cytochrome P450 2D6 (CYP2D6) variants representing all possible amino acid exchanges at two important enzyme's residues were expressed and individually analyzed to investigate their influence on regioselective steroid hydroxylation. Steroids represent a substrate class atypical for wildtype CYP2D6. Employing this strategy CYP2D6 variants with improved activity and variants with altered region-preference were identified and characterized.

Biotransformations of progesterone by Chlorella spp.

Thirty-eight strains of Chlorella spp. were used as bioreactors on progesterone. Fourteen strains were ineffective whilst the others biotransformed the substrate. The observed bioreactions for progesterone were the hydroxylation, the reduction and the side-chain degradation. The kinds of biotransformation seem to fit the actual classification of the strains.

Biotransformation of progesterone by the green alga Chlorella emersonii C211-8H

2β-Hydroxyprogesterone, 6β-hydroxyprogesterone, 9α-hydroxyprogesterone, 14α-hydroxyprogesterone, 16α-hydroxyprogesterone and 21-hydroxyprogesterone are the main bioproducts in the progesterone bioconversion by axenic cultures of Chlorella emersonii C211-8

Direct transformation of steroidal ethers into ketones by dimethyldioxirane

Treatment of the methyl- and benzyl ethers of 3-hydroxy steroids with a solution of dimethyldioxirane resulted in the formation of the corresponding ketones in high yield.