Microbial hydroxylation of 13β-ethyl-4-gonene-3,17-dione

Jekkel, Antónia; Ilkőy, Éva; Horváth, Gyula; Pallagi, István; Sütő, J.; Ambrus, Gábor

doi:10.1016/s1381-1177(98)00097-6

Cited by 14 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The enzymatically catalyzed reactions can replace several separate chemical steps in the synthesis of natural hormones and steroidal drugs such as corticosteroids and progestogens (reviewed in Fernandes et al, 2003). Specifically, the 11␣-hydroxyl derivatives of steroids represent commercially important intermediates in the production of contraceptive drugs (Jekkel et al, 1998) and synthetic glucocorticoid steroids used as anti-inflammatory, immunosuppressive, and anti-allergic drugs (Fernandes et al, 2003;Mahato and Garai, 1997) by offering access to the otherwise inaccessible site of the steroid molecule, which can then be chemically converted to the active form (Hogg et al, 1955).…”

Section: Introductionmentioning

confidence: 99%

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Petrič

Hakki

Bernhardt

et al. 2010

Journal of Biotechnology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Petrič

Hakki

Bernhardt

et al. 2010

Journal of Biotechnology

View full text Add to dashboard Cite

“…The corresponding biochemical processes are used to produce various steroidogenic compounds, including 11b-, 11a-, 15a-and 16a-hydroxylated products. These compounds are mainly used for the production of adrenal cortex hormones and their analogues [4,6,7]. They have a broad therapeutic application in contraceptives, antiinflammatory, immunosuppressive, anabolic, and diuretic drugs.…”

Section: Introductionmentioning

confidence: 99%

Molecular Evolution of a Steroid Hydroxylating Cytochrome P450 Using a Versatile Steroid Detection System for Screening

Virus

Bernhardt

2008

Lipids

View full text Add to dashboard Cite

Molecular evolution is a powerful tool for improving or changing activities of enzymes for their use in biotechnological processes. Cytochromes P450 are highly interesting enzymes for biotechnological purposes because they are able to hydroxylate a broad variety of substrates with high regio- and stereoselectivity. One promising steroid hydroxylating cytochrome P450 for biotechnological applications is CYP106A2 from Bacillus megaterium ATCC 13368. It is one of a few known bacterial cytochromes P450 able to transform steroids such as progesterone and 11-deoxycortisol. CYP106A2 can be easily expressed in Escherichia coli with a high yield and can be reconstituted using the adrenal redox proteins, adrenodoxin and adrenodoxin reductase. We developed a simple screening assay for this system and performed random mutagenesis of CYP106A2, yielding variants with improved 11-deoxycortisol and progesterone hydroxylation activity. After two generations of directed evolution, we were able to improve the k (cat)/K (m) of the 11-deoxycortisol hydroxylation by a factor of more than four. At the same time progesterone conversion was improved about 1.4-fold. Mapping the mutations identified in catalytically improved CYP106A2 variants into the structure of a CYP106A2 model suggests that these mutations influence the mobility of the F/G loop, and the interaction with the redox partner adrenodoxin. The results show the evolution of a soluble steroid hydroxylase as a potential new catalyst for the production of steroidogenic compounds.

show abstract

“…Biotransformation of 3β-hydroxy-17β-carboxyethyl-5βandrostenol (88) using T. pyriformis resulted in the mixture of 3β,14α-dihydroxy-17β-carboxyethyl-5β-androstenol (89, 9%) with 9α,14αdihydroxy derivative (90, 12%) and two minor products 14α,15α-dihydroxy (91) and 15β-hydroxy (92). Compound 92 was identified as a product of biotransformation using A. elegans, M. griseocyamus, and Zygodesmus sp.…”

Section: Microbiological Transformations Of Steroidsmentioning

confidence: 99%

“…In the literature, several species of fungi belonging to the genera Aspergillus, Fusarium, Mortierella, and Penicillium and capable of hydroxylating various steroids in C-15 have been described. For example, Jekkel et al [92] described that more than 3000 fungi hydroxylate 13β-ethyl-4-gonene-3,17-dione (187) in C-15 position, the genus being Fusarium, particularly F. nivale; the fungus preferentially hydroxylated 187 with an α orientation in C-15 (15α-hydroxy-13β-ethyl-4-gonene-3,17-dione, 188, 77%) and C-7β (7β,15α-dihydroxy-13β-ethyl-4-gonene-3,17diona, 189). On the other hand, the biotransformation of 187 using Mortierella pusilla produced 188, 190 (10β-hydroxy-13β-ethyl-4-gonene-3,17-dione) and 191 (6β-hydroxy-13β-ethyl-4-gonene-3,17-dione) (Figure 24).…”

Section: Microbiological Transformations Of Steroidsmentioning

confidence: 99%

Biotransformation of Steroids Using Different Microorganisms

Cano-Flores¹,

Gómez²,

Ramos³

2020

Chemistry and Biological Activity of Steroids

View full text Add to dashboard Cite

The introduction of a hydroxyl group "biohydroxylation" in the steroid skeleton is an important step in the synthesis of new steroids used physiologically as hormones and active drugs. There are currently about 300 known steroid drugs whose production constitutes the second category within the pharmaceutical market after antibiotics. Several biotransformations at industrial scale have been applied in the production of steroid hormones and drugs, which have functionalized different types of raw materials by means of chemo-, regio-, and stereoselective reactions (hydroxylation, Baeyer-Villiger oxidation, oxidation reactions, reduction of group carbonyl, isomerization, and Michael additions, condensation reactions, among others). In Green Chemistry, biotransformations are an important chemical methodology toward more sustainable industrial processes.

show abstract

Microbial hydroxylation of 13β-ethyl-4-gonene-3,17-dione

Cited by 14 publications

References 0 publications

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application

Molecular Evolution of a Steroid Hydroxylating Cytochrome P450 Using a Versatile Steroid Detection System for Screening

Biotransformation of Steroids Using Different Microorganisms

Contact Info

Product

Resources

About