XIV- XXIX
3. Conclusions
The biotransformation processes of different steroid compounds described in this review, although not exhaustive, aim to highlight the importance of biotrans- formation through different microorganisms, as a useful chemical-biological tool for obtaining novel derivatives for research purpose and as industrial applica- tions. An example includes obtaining steroid compounds for the pharmaceutical industry.
Biotransformation of steroids has been implemented in an important way in the partial synthesis of new steroids, for their evaluation as hormones and drugs. Currently, there is a wide variety of steroids used as diuretics, anabolic, anti-inflammatory, antiandrogenic, anticontraceptive, antitumor, among other applications. Chemical functionalization in different carbon atoms of the sternum skeleton is related to the biological activity of the molecule. This is why microbiological transformations play an important role in obtaining these compounds through chemical transformations, such as the oxidation of hydroxyl group at C-3 and C-17, isomerization of the double bond Δ5(6) to Δ4(5), hydrogenation of double bonds Δ1(2) and Δ4(5), and reduction of the carbonyl group at C-17 and C-20 with β orientation. Biohydroxylations performed in different positions of the steroid skeleton—C-11α, C-11β, C-15β, and C-16α—using dif- ferent species of fungi of the genera Rhizopus, Aspergillus, Curvularia, Cunninghamella, and Streptomyces with high yields are an important chemical transformation in many synthesis schemes of new steroids with a determined biological activity.
Hydroxylation of steroids—progesterone, testosterone, 17α-methyltestosterone, and 4-androsten-3,17-dione—presenting the 4-en-3-one system, proceeds with a high stereo- and regioselectivity in the C-6 and C-11 positions, with a β orienta- tion in C-6 and α orientation in C-11. The presence of the methyl group in C-10 is necessary for the hydroxylation in C-11, as can be seen in the derivatives of 19-nortesterone.
The interest in the biotransformation of steroid compounds has been increasing in recent years, due to the obtaining of new and useful pharmacologically active compounds. In addition to the development of new genetically modified strains, there is an increase in the availability of immobilized enzymes and the manipula- tion of culture media.
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Author details
Arturo Cano-Flores*, Javier Gómez and Rigoberto Ramos
Laboratorio de Biotransformaciones y Química de Productos Naturales, L-314, Facultad de Estudios Superiores Zaragoza, UNAM, México, D.F., Mexico
*Address all correspondence to: [email protected]
Biotransformation of steroids proceeds with low to moderate yields in general.
One of the main causes is their low solubility in water. Currently, methodologies are developed that allow the incorporation of chemicals—surfactants, ionic liquids, cyclodextrins, liposomes, among others—that contribute to improve the yields of each biotransformation process and the processes friendly to the environment.
Acknowledgements
A la Carrera de Biología, FES-Zaragoza, UNAM. Ms. Fabiola Cano thank for her suggestions and comments toward improving the manuscript.
Similarly, B. bassiana, A. ochraceus, Colletotrichum lagenarium, and Sporotrichum sulfurreducens gave a biotransformed product 232 [104]. Absidia glauca metabolized 229 in compounds 230, and 236–237 [105]. In contrast, the biotransformation of 229 using A. coerula yielded 239 along with 7α-hydroxydianabol (240) [106], while by using B cinerea, 237 was obtained as the only product (Figure 31) [107].
Methasterone (241) is a synthetic anabolic steroid, known to gain muscle mass. Microbial transformation of 241 using M phaseolina yielded 17β-hydroxy- 17α(hydroxymethyl)-2α-methyl-5α-androstane-3,6-dione (242), while by using C.
blakesleeana, 7α-hydroxymethasterone (243, 2.0%), 7α,16β-dihydroxymethasterone (244, 0.7%), 5α,12β-dihydroxymethasterone (245, 1.0%), 7α,12β-
dihydroxymethasterone (246, 1.5%), and 7α,9α-dihydroxy-methasterone (247, 0.5%) were obtained. Incubation of 241 with Fusarium lini yielded different metabolites with dehydrogenation in ring A and D: 6β,17β-dihydroxy-2,17α-dimethyl-5α-androst-1,4- diene-3-one (248, 1.0%), 15α,17β-dihydroxy-2α,17α-dimethyl-5α-androst-1,4-diene- 3-one (249, 0.6%), 6β,17β-dihydroxy-2,17α-dimethylandrost-1,4-diene-3-one (250, 0.4%), 14α,15α-dihydroxy-2,17-dimethyl-5α-androst-1,4,16-trien-3-one (251, 0.3%), 17β-hydroxy-2,17α-dimethyl-5α-androst-5α-1,4-dien-3,6-dione (252, 0.3%), and 17β-hydroxy-2,17α-dimethyl-5α-androst-1,4-dien-3-one (253, 1.0%) (Figure 32) [108].
3. Conclusions
The biotransformation processes of different steroid compounds described in this review, although not exhaustive, aim to highlight the importance of biotrans- formation through different microorganisms, as a useful chemical-biological tool for obtaining novel derivatives for research purpose and as industrial applica- tions. An example includes obtaining steroid compounds for the pharmaceutical industry.
Biotransformation of steroids has been implemented in an important way in the partial synthesis of new steroids, for their evaluation as hormones and drugs. Currently, there is a wide variety of steroids used as diuretics, anabolic, anti-inflammatory, antiandrogenic, anticontraceptive, antitumor, among other applications. Chemical functionalization in different carbon atoms of the sternum skeleton is related to the biological activity of the molecule. This is why microbiological transformations play an important role in obtaining these compounds through chemical transformations, such as the oxidation of hydroxyl group at C-3 and C-17, isomerization of the double bond Δ5(6) to Δ4(5), hydrogenation of double bonds Δ1(2) and Δ4(5), and reduction of the carbonyl group at C-17 and C-20 with β orientation. Biohydroxylations performed in different positions of the steroid skeleton—C-11α, C-11β, C-15β, and C-16α—using dif- ferent species of fungi of the genera Rhizopus, Aspergillus, Curvularia, Cunninghamella, and Streptomyces with high yields are an important chemical transformation in many synthesis schemes of new steroids with a determined biological activity.
Hydroxylation of steroids—progesterone, testosterone, 17α-methyltestosterone, and 4-androsten-3,17-dione—presenting the 4-en-3-one system, proceeds with a high stereo- and regioselectivity in the C-6 and C-11 positions, with a β orienta- tion in C-6 and α orientation in C-11. The presence of the methyl group in C-10 is necessary for the hydroxylation in C-11, as can be seen in the derivatives of 19-nortesterone.
The interest in the biotransformation of steroid compounds has been increasing in recent years, due to the obtaining of new and useful pharmacologically active compounds. In addition to the development of new genetically modified strains, there is an increase in the availability of immobilized enzymes and the manipula- tion of culture media.
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Author details
Arturo Cano-Flores*, Javier Gómez and Rigoberto Ramos
Laboratorio de Biotransformaciones y Química de Productos Naturales, L-314, Facultad de Estudios Superiores Zaragoza, UNAM, México, D.F., Mexico
*Address all correspondence to: [email protected]
Biotransformation of steroids proceeds with low to moderate yields in general.
One of the main causes is their low solubility in water. Currently, methodologies are developed that allow the incorporation of chemicals—surfactants, ionic liquids, cyclodextrins, liposomes, among others—that contribute to improve the yields of each biotransformation process and the processes friendly to the environment.
Acknowledgements
A la Carrera de Biología, FES-Zaragoza, UNAM. Ms. Fabiola Cano thank for her suggestions and comments toward improving the manuscript.
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10.1016/S0039-128X(99)00109-9
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Glucocorticoids and mineralocorticoids.
In: Bader M, editor. Cardiovascular Hormone Systems: From Molecular Mechanisms to Novel Therapeutics.
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Co; 2009. pp. 1-64
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2009;34:169-177. DOI: 10.1016/j.
psyneuen.2009.06.004
[2] Funder JW. Minireview: Aldosterone and mineralocorticoid receptors: Past, present, and future. Endocrinology.
2010;151:5098-5102. DOI: 10.1210/
en.2010-0465
[3] Fernandez P, Cruz A, Angelova B, Pinheiro HM, Cabral JMS.
Microbial conversion of steroid compounds: Recent developments.
Enzyme and Microbial Technology.
2003;32:688-705. DOI: 10.1016/
S0141-0229(03)00029-2
[4] Hogg JA. Steroids, steroids
community and Upjohn in perspective:
A profile of innovation. Steroids.
1992;257:593-616
[5] Sedlaczek L. Biotransformations of steroids. Critical Reviews in Biotechnology. 1988;7:187-236. DOI:
10.3109/07388558809146602
[6] Ko D-H, Heiman AS, Chen M, Lee HJ. New steroidal anti-inflammatory antedrugs: Methyl 21-desoxy-21-chloro- 11β,17α-dihydroxy-3,20-dioxo-1,4- pregnadiene-16α-carboxylate, methyl 21-desoxy-21-chloro-11β-hydroxy-3,20- dioxo-1,4-pregnadiene-16α-carboxylate, and their 9α-fluoro derivatives. Steroids.
2000;65:210-218
[7] Fragkaki AG, Angelis YS, Koupparis M, Tsantili-Kakoulidou A, Kokotos G, Georgakopoulus C. Structural
characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities: Applied modifications in the steroidal structure.
Steroids. 2009;74:172-197. DOI:
10.1016/j.steroids.2008.10.016
[8] Agoston ES, Hastcher MA, Kensler TW, Posner GH. Vitamin D analogs as anti-carcinogenic agents.
Anti-Cancer Agents in Medicinal Chemistry. 2006;6:53-71. DOI:
10.2174/187152006784111369
[9] Tuba Z, Barden CW, Dancsi A, Francsics-Czinege E, Molnar EC, Csorgei J, et al. Synthesis and biological activity of a new progestogen,
16-methylene-17α-hydroxy-18-methyl- 19-norpregn-4-ene-3,20-dione acetate.
Steroids. 2000;65:266-274. DOI:
10.1016/S0039-128X(99)00109-9
[10] Siemes C, Visser LE, De-Jong FH, Jan-Willem Coebergh W, Uitterlinden AG. Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer. Steroids.
2010;75:1024-1032. DOI: 10.1016/j.
steroids.2010.07.001
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jsbmb.2006.11.019
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In: Parish EJ, Nes WD, editors.
Biochemistry and Function of Sterols.
Boca Raton, FL: CRC Press; 1987.
pp. 23-53
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Glucocorticoids and mineralocorticoids.
In: Bader M, editor. Cardiovascular Hormone Systems: From Molecular Mechanisms to Novel Therapeutics.
Weinheim: Wiley-VCH Verlag GmbH &
Co; 2009. pp. 1-64
[14] Chung SK, Ryoo CH, Yang HW, Shim JY, Kang MG, Lee KW, et al.
References Synthesis and bioactivites of steroids
derivatives as antifungal agents.
Tetrahedron. 1998;52:15899-15914. DOI:
10.1016/S0040-4020(98)01000-X
[15] Suzuki K, Nakata T, Shimizu T, Enomoto K. Anti-obesity agents. US Patent 5,846,962; 1998
[16] Dombrowski AW, Hazuda DJ, Polishook JD, Felock PJ, Singh SB, Zink DL. HIV-integrase-inhibitors. WO Patent 0036132; 2000
[17] Athan D, Svasti J, Kittakoop P, Pittayakhachonwut D, Tanticharpen M, Thebtaranoth Y. Antiviral isoflavonoid sulfate and steroidal glycoside
from the fruits of Solanum torvum.
Phytochemistry. 2002;59:459-463. DOI:
10.1016/S0031-9422(01)00417-4
[18] Rupprecht R, Holsboer F.
Neuoroactive steroids: Mechanisms of action and neuropsychopharmacology perspectivs. Trends in Neurosciences.
1999;22:410-416. DOI: 10.1016/
S0166-2236(99)01399-5
[19] Mellon SH, Griffin LD.
Neurosteroids: Biochemistry and clinical significance. Trends in Endocrinology and Metabolism.
2002;13:35-43. DOI: 10.1016/
S1043-2760(01)00503-3
[20] Baulieu E-E, Schumacher M.
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[21] Fernandez P, Cabral JMS. Steroid bioconversion. In: Flickinger M, editor. Enciclopedia of Industrial Biotechnology: Bioprocess,
Bioseparation, and Cell Technology.
New York: John Wiley & Sons, Inc.;
2010. pp. 1-32
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Microbiology and Biotechnology.
2012;94:1423-1447. DOI:
10.1007/978-1-4939-7183-1
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steroids.2018.01.007
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Recent Patents on Biotechnology.
2009;3:141-153
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