Please use this identifier to cite or link to this item: doi:10.22028/D291-28646
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Title: High-yield C11-oxidation of hydrocortisone by establishment of an efficient whole-cell system in Bacillus megaterium
Author(s): König, Lisa
Hartz, Philip
Bernhardt, Rita
Hannemann, Frank
Language: English
Title: Metabolic engineering
Volume: 55
Startpage: 59
Endpage: 67
Publisher/Platform: Elsevier
Year of Publication: 2019
Publikation type: Journal Article
Abstract: Steroidal compounds are one of the most widely marketed pharmaceutical products. Chemical synthesis of steroidal compounds faces many challenges, including the requirement for multiple chemical steps, low yield and selectivity in several synthesis steps, low profitability and the production of environmental pollutants. Consequently, in recent decades there has been growing interest in the use of microbial systems to produce pharmaceutical compounds. Several microbial systems have recently been developed for the microbial synthesis of the glucocorticoid hydrocortisone, which serves as a key intermediate in the production of several other pharmaceutically important steroidal compounds. In this study, we sought to establish an efficient, microbial-based system, for the conversion of hydrocortisone into cortisone. To this end, we developed a strategy for high-yield cortisone production based on ectopic expression of the guinea-pig 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) in Bacillus megaterium. We screened different constructs, containing a variety of promoters tailored for B. megaterium, and created modified versions of the enzyme by protein engineering to optimize cortisone yield. Furthermore, we utilized co-expression of an alcohol dehydrogenase to promote NADP+ regeneration, which significantly improved 11β-HSD1 activity. The process thereby developed was found to show a remarkably high regioselectivity of >95% and to generate cortisone yields of up to 13.65 g L-1 d-1, which represents a ∼1000-fold improvement over the next-best reported system. In summary, we demonstrate the utility of B. megaterium MS941 as a suitable host for recombinant protein production and its high potential for industrial steroid production.
DOI of the first publication: 10.1016/j.ymben.2019.06.005
URL of the first publication:
Link to this record: hdl:20.500.11880/27676
ISSN: 1096-7184
Date of registration: 6-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Bruce Morgan
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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