ArticleMicrobial cell factories2015
A recombinant CYP11B1 dependent Escherichia coli biocatalyst for selective cortisol production and optimization towards a preparative scale.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 35 citations in OpenAlex.
- Functional studies on the cytochrome P450 splice variants CYP4F3A and CYP4F3B unveil the basis for their distinct physiological functions.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
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- Production of 11α-hydroxysteroids from sterols in a single fermentation step by Mycolicibacterium smegmatis.Microbial biotechnology · 2021Article
- Engineering the Steroid Hydroxylating System fromMicroorganisms · 2021Article
- Efficient production of oxidized terpenoids via engineering fusion proteins of terpene synthase and cytochrome P450.Metabolic engineering · 2021Article
- Identification and expression of the 11β-steroid hydroxylase from Cochliobolus lunatus in Corynebacterium glutamicum.Microbial biotechnology · 2019Article
- Analysis of In Vivo Activity of the Bovine Cholesterol Hydroxylase/Lyase System Proteins Expressed in Escherichia coli.Molecular biotechnology · 2019Article
- Human Enzymes for Organic Synthesis.Angewandte Chemie (International ed. in English) · 2018Review
- A Fungal P450 Enzyme from Thanatephorus cucumeris with Steroid Hydroxylation Capabilities.Applied and environmental microbiology · 2018Article
- Cell foundry with high product specificity and catalytic activity for 21-deoxycortisol biotransformation.Microbial cell factories · 2017Article
- A CYP21A2 based whole-cell system in Escherichia coli for the biotechnological production of premedrol.Microbial cell factories · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman mitochondrial CYP11B1 catalyzes a one-step regio- and stereoselective 11β-hydroxylation of 11-deoxycortisol yielding cortisol which constitutes not only the major human stress hormone but also represents a commercially relevant therapeutic drug due to its anti-inflammatory and immunosuppressive properties. Moreover, it is an important intermediate in the industrial production of synthetic pharmaceutical glucocorticoids. CYP11B1 thus offers a great potential for biotechnological application in large-scale synthesis of cortisol. Because of its nature as external monooxygenase, CYP11B1-dependent steroid hydroxylation requires reducing equivalents which are provided from NADPH via a redox chain, consisting of adrenodoxin reductase (AdR) and adrenodoxin (Adx).
resultsWe established an Escherichia coli based whole-cell system for selective cortisol production from 11-deoxycortisol by recombinant co-expression of the demanded 3 proteins. For the subsequent optimization of the whole-cell activity 3 different approaches were pursued: Firstly, CYP11B1 expression was enhanced 3.3-fold to 257 nmol∗L(-1) by site-directed mutagenesis of position 23 from glycine to arginine, which was accompanied by a 2.6-fold increase in cortisol yield. Secondly, the electron transfer chain was engineered in a quantitative manner by introducing additional copies of the Adx cDNA in order to enhance Adx expression on transcriptional level. In the presence of 2 and 3 copies the initial linear conversion rate was greatly accelerated and the final product concentration was improved 1.4-fold. Thirdly, we developed a screening system for directed evolution of CYP11B1 towards higher hydroxylation activity. A culture down-scale to microtiter plates was performed and a robot-assisted, fluorescence-based conversion assay was applied for the selection of more efficient mutants from a random library.
conclusionsUnder optimized conditions a maximum productivity of 0.84 g cortisol∗L(-1)∗d(-1) was achieved, which clearly shows the potential of the developed system for application in the pharmaceutical industry.
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