Biotransformation of progesterone by Absidia griseolla var. igachii and Rhizomucor pusillus

Habibi, Zohreh; Yousefi, Maryam; Ghanian, Shamim; Mohammadi, Mehdi; Ghasemi, Sabrieh

doi:10.1016/j.steroids.2012.08.010

Cited by 22 publications

(14 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hydroxylation at C-7 produces very useful hydroxysteroids of pharmacological value (32,33). Although many fungi have been reported to mediate 7-hydroxylation of steroids (34)(35)(36)(37)(38)(39)(40)(41)(42), low stereoselectivity (7␣/7␤) (38,41) and side hydroxylation reactions (37,42) have often been observed, thus presenting great challenges in developing highly regio-and stereoselective 7-hydroxylation processes of steroidal compounds. CYP5150AP3 favors the 7␤-hydroxylation of 11-deoxycortisol, a 3-keto-4-en-C 21 steroid, and may serve as a starting point for addressing these challenges.…”

Section: Discussionmentioning

confidence: 99%

Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation

Lü

Feng

Chen

et al. 2019

Appl Environ Microbiol

View full text Add to dashboard Cite

In this study, we identified two P450 enzymes (CYP5150AP3 and CYP5150AN1) from Thanatephorus cucumeris NBRC 6298 by combination of transcriptome sequencing and heterologous expression in Pichia pastoris. The biotransformation of 11-deoxycortisol and testosterone by Pichia pastoris whole cells coexpressing the cyp5150ap3 and por genes demonstrated that the CYP5150AP3 enzyme possessed steroidal 7β-hydroxylase activities toward these substrates, and the regioselectivity was dependent on the structures of steroidal compounds. CYP5150AN1 catalyzed the 2β-hydroxylation of 11-deoxycortisol. It is interesting that they display different regioselectivity of hydroxylation from that of their isoenzyme, CYP5150AP2, which possesses 19- and 11β-hydroxylase activities. IMPORTANCE The steroidal hydroxylases CYP5150AP3 and CYP5150AN1 together with the previously characterized CYP5150AP2 belong to the CYP5150A family of P450 enzymes with high amino acid sequence identity, but they showed completely different regioselectivities toward 11-deoxycortisol, suggesting the regioselectivity diversity of steroidal hydroxylases of CYP5150 family. They are also distinct from the known bacterial and fungal steroidal hydroxylases in substrate specificity and regioselectivity. Biocatalytic hydroxylation is one of the important transformations for the functionalization of steroid nucleus rings but remains a very challenging task in organic synthesis. These hydroxylases are useful additions to the toolbox of hydroxylase enzymes for the functionalization of steroids at various positions.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation

Lü

Feng

Chen

et al. 2019

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…Microbial hydroxylation of 102 by A. griseola produced two hydroxylated pregnane identified as 6β,14α-dihydroxyprogesterone (103) and 7α,14α-dihydroxyprogesterone (104). R. pusillus produced 6β,11α-dihydroxyprogesterone (105) with excellent yield (65.5%) and 7α,14αdihydroxyprogesterone (106) (Figure 7) [51]. Industry, which is carried by different microorganisms, such as different species of Curvularia spp., Cunninghamella spp.…”

Section: Steroidsmentioning

confidence: 99%

Microorganisms as Biocatalysts and Enzyme Sources

Cano-Flores¹,

Gómez²,

Escalona-Torres³

et al. 2020

Microorganisms

View full text Add to dashboard Cite

Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids, flavonoids, steroids, steroidal saponins, and sesquiterpenoids. They offer efficient and economical ways to produce semisynthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio-, and stereospecific hydroxylations of diverse substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive compounds, in order to obtain biologically active molecules with diverse structural features. In green chemistry, biotransformations are an important chemical methodology toward more sustainable industrial processes.

show abstract

“…Several steroids are used as anabolic, contraceptive, anti-androgenic, anti-inflammatory, and anti-cancer agents. Microbial hydroxylation of steroids is an efficient method for the synthesis of new hydroxysteroids with high stereo- and regio-selectivity, and for study of the steroidal metabolism [ 1 , 3 – 5 ]. The bioconversion of steroids was initiated in 1950.…”

Section: Introductionmentioning

confidence: 99%

New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

et al. 2016

View full text Add to dashboard Cite

Microbial transformation of the anti-inflammatory steroid medrysone (1) was carried out for the first time with the filamentous fungi Cunninghamella blakesleeana (ATCC 8688a), Neurospora crassa (ATCC 18419), and Rhizopus stolonifer (TSY 0471). The objective was to evaluate the anti-inflammatory potential of the substrate (1) and its metabolites. This yielded seven new metabolites, 14α-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (2), 6β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (3), 15β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (4), 6β,17α-dihydroxy-6α-methylpregn-4-ene-3,11,20-trione (5), 6β,20S-dihydroxy-6α-methylpregn-4-ene-3,11-dione (6), 11β,16β-dihydroxy-6α-methylpregn-4-ene-3,11-dione (7), and 15β,20R-dihydroxy-6α-methylpregn-4-ene-3,11-dione (8). Single-crystal X-ray diffraction technique unambiguously established the structures of the metabolites 2, 4, 6, and 8. Fungal transformation of 1 yielded oxidation at the C-6β, -11β, -14α, -15β, -16β positions. Various cellular anti-inflammatory assays, including inhibition of phagocyte oxidative burst, T-cell proliferation, and cytokine were performed. Among all the tested compounds, metabolite 6 (IC50 = 30.3 μg/mL) moderately inhibited the reactive oxygen species (ROS) produced from zymosan-induced human whole blood cells. Compounds 1, 4, 5, 7, and 8 strongly inhibited the proliferation of T-cells with IC50 values between <0.2–10.4 μg/mL. Compound 7 was found to be the most potent inhibitor (IC50 < 0.2 μg/mL), whereas compounds 2, 3, and 6 showed moderate levels of inhibition (IC50 = 14.6–20.0 μg/mL). Compounds 1, and 7 also inhibited the production of pro-inflammatory cytokine TNF-α. All these compounds were found to be non-toxic to 3T3 cells (mouse fibroblast), and also showed no activity when tested against HeLa (human epithelial carcinoma), or against PC3 (prostate cancer) cancer cell lines.

show abstract

Biotransformation of progesterone by Absidia griseolla var. igachii and Rhizomucor pusillus

Cited by 22 publications

References 9 publications

Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation

Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation

Microorganisms as Biocatalysts and Enzyme Sources

New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

Contact Info

Product

Resources

About