Bibliographic Details
| Title: |
Pregnenolone and progesterone production from natural sterols using recombinant strain of Mycolicibacterium smegmatis mc2 155 expressing mammalian steroidogenesis system. |
| Authors: |
Karpov, Mikhail1 (AUTHOR) mikhail.v.karpov@mail.ru, Strizhov, Nicolai1 (AUTHOR), Novikova, Ludmila2 (AUTHOR), Lobastova, Tatyana1 (AUTHOR), Khomutov, Sergey1 (AUTHOR), Shutov, Andrei1 (AUTHOR), Kazantsev, Alexey3 (AUTHOR), Donova, Marina1 (AUTHOR) donova@ibpm.pushchino.ru |
| Source: |
Microbial Cell Factories. 4/9/2024, Vol. 23 Issue 1, p1-14. 14p. |
| Subject Terms: |
*PREGNENOLONE, *STEROLS, *STEROID hormones, *FERREDOXIN-NADP reductase, *CHOLESTEROL hydroxylase, *ADRENAL cortex, *PROGESTERONE receptors, *PROGESTERONE, *HYDROXYCHOLESTEROLS |
| Abstract: |
Background: Pregnenolone and progesterone are the life-important steroid hormones regulating essential vital functions in mammals, and widely used in different fields of medicine. Microbiological production of these compounds from sterols is based on the use of recombinant strains expressing the enzyme system cholesterol hydroxylase/C20-C22 lyase (CH/L) of mammalian steroidogenesis. However, the efficiency of the known recombinant strains is still low. New recombinant strains and combination approaches are now needed to produce these steroid hormones. Results: Based on Mycolicibacterium smegmatis, a recombinant strain was created that expresses the steroidogenesis system (CYP11A1, adrenodoxin reductase, adrenodoxin) of the bovine adrenal cortex. The recombinant strain transformed cholesterol and phytosterol to form progesterone among the metabolites. When 3-methoxymethyl ethers of sterols were applied as bioconversion substrates, the corresponding 3-ethers of pregnenolone and dehydroepiandrosterone (DHEA) were identified as major metabolites. Under optimized conditions, the recombinant strain produced 85.2 ± 4.7 mol % 3-methoxymethyl-pregnenolone within 48 h, while production of 3-substituted DHEA was not detected. After the 3-methoxymethyl function was deprotected by acid hydrolysis, crystalline pregnenolone was isolated in high purity (over 98%, w/w). The structures of steroids were confirmed using TLC, HPLC, MS and 1H- and 13C-NMR analyses. Conclusion: The use of mycolicybacteria as a microbial platform for the expression of systems at the initial stage of mammalian steroidogenesis ensures the production of valuable steroid hormones—progesterone and pregnenolone from cholesterol. Selective production of pregnenolone from cholesterol is ensured by the use of 3-substituted cholesterol as a substrate and optimization of the conditions for its bioconversion. The results open the prospects for the generation of the new microbial biocatalysts capable of effectively producing value-added steroid hormones. [ABSTRACT FROM AUTHOR] |
|
Copyright of Microbial Cell Factories is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
