Abstract
Two-step one-pot microbial transformation enables obtaining of valuable steroids that are difficult to produce chemically. Here we describe a method for obtaining 11α-hydroxyandrost-4-ene-3,17-dione (11α-HAD) from cheap and available natural sterols (phytosterols or cholesterol).
11α-HAD is a primary adrenal steroid in mammals and also a key precursor in the syntheses of halogenated corticoids. Conventional routes for its obtaining are based on chemical synthesis, or microbial hydroxylation of androst-4-ene-3,17-dione (AD). AD in turn is produced primarily with microbial biotransformation of natural sterols by some actinobacteria.
Consequent bioconversions of sterols using two microbial strains in one bioreactor vessel without separation and purification of AD provides high yield of 11α-HAD. At the first fermentation step, phytosterol is converted to AD with Mycobacterium neoaurum NRRL 3805B, or relative strains, to yield about 70% (mol/mol). At the second step, AD is almost fully (98%) hydroxylated at the position 11α with Aspergillus ochraceus VKM F-830, or other suitable organisms, in the same bioreactor. At the average, 30% (w/w) of the high-purity crystalline 11α-HAD can be obtained.
The method can be exploited for production of 11α-HAD for practical use.
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Acknowledgment
This work was supported by Russian Science Foundation grant (14-24-00169) and ERA-IB (Project: MySterI).
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Dovbnya, D., Khomutov, S., Kollerov, V., Donova, M.V. (2017). Obtaining of 11α-Hydroxyandrost-4-ene-3,17-dione from Natural Sterols. In: Barredo, JL., Herráiz, I. (eds) Microbial Steroids. Methods in Molecular Biology, vol 1645. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7183-1_18
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DOI: https://doi.org/10.1007/978-1-4939-7183-1_18
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