当前位置： SCI文献检索 > JOURNAL OF BIOTECHNOLOGY期刊下所有文献 > Human 20α-hydroxysteroid dehydrogenase (AKR1C1)-dependent biotransformation with recombinant fission yeast Schizosaccharomyces pombe.

Human 20α-hydroxysteroid dehydrogenase (AKR1C1)-dependent biotransformation with recombinant fission yeast Schizosaccharomyces pombe.

Abstract：

:While phase I and phase II drug metabolites are important for drug development and toxicity studies, e.g. in the context of metabolites in safety testing (MIST), they are often not commercially available and their classical chemical synthesis can be cumbersome. Therefore, a biotechnological production of drug metabolites using microorganisms that recombinantly express human enzymes has been established in recent years. However, no whole-cell biotransformations that make use of human aldo-keto reductases (AKRs) have yet been reported. In this study, we have functionally expressed human AKR1C1 (20α-hydroxysteroid dehydrogenase) in the fission yeast Schizosaccharomyces pombe and demonstrate the ability of the resulting yeast strain to efficiently catalyze the reduction of progesterone or dydrogesterone to 20α-dihydroprogesterone (20α-DHP) and 20α-dihydrodydrogesterone (20α-DHD), respectively. The formation of any by-products or the occurrence of a back reaction were not detected. Seven other steroids with a 20-keto group (pregnenolone, 17α-hydroxyprogesterone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, and aldosterone) were not reduced by this system. At shaking flask scale we obtained conversion rates of 90 (±26) μM/d 20α-DHP and 244 (±93) μM/d 20α-dihydrodydrogesterone (20α-DHD), respectively. In a fed-batch fermentation under optimized reaction conditions an average 20α-DHP production rate of 300 μM/d was determined for a total biotransformation time of 72 h. We thus established an AKR-dependent whole-cell biotransformation process that can be used for production of human AKR metabolites on a large scale.

journal_name

J Biotechnol

journal_title

Journal of biotechnology

authors

Naumann JM,Messinger J,Bureik M

doi

10.1016/j.jbiotec.2010.08.004

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

161-70

issue

1

eissn

0168-1656

issn

1873-4863

pii

S0168-1656(10)00385-8

journal_volume

150

pub_type

杂志文章

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