Open AccessEfficient conversion of 11‐deoxycortisol to cortisol (hydrocortisone) by recombinant fission yeast Schizosaccharomyces pombe
Author(s) -
Drăgan CălinAurel,
Zearo Silvia,
Hannemann Frank,
Bernhardt Rita,
Bureik Matthias
Publication year - 2005
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1016/j.femsyr.2004.12.001
Subject(s) - steroid 11 beta hydroxylase , schizosaccharomyces pombe , yeast , biology , biotransformation , aldosterone , aldosterone synthase , enzyme , biochemistry , cytochrome p450 , steroid , saccharomyces cerevisiae , endocrinology , renin–angiotensin system , hormone , blood pressure
Genetically engineered microorganisms are being increasingly used for the industrial production of complicated chemical compounds such as steroids; however, there have been few reports on the use of the fission yeast Schizosaccharomyces pombe for this purpose. We previously have demonstrated that this yeast is a unique host for recombinant expression of human CYP11B2 (aldosterone synthase), and here we report the functional production of human CYP11B1 (steroid 11β‐hydroxylase) in S. pombe using our new integration vector pCAD1. In the human adrenal, the mitochondrial cytochrome P450 enzyme CYP11B1 catalyses the conversion of 11‐deoxycortisol to cortisol, a key reaction in cortisol biosynthesis that in addition is of fundamental interest for the technical synthesis of glucocorticoids. We observed that the endogenous mitochondrial electron transport system detected previously by us is capable of supplying this enzyme with the reducing equivalents necessary for steroid hydroxylation activity. Under optimised cultivation conditions the transformed yeasts show in vivo the inducible ability to efficiently and reliably convert deoxycortisol to cortisol at an average rate of 201 μM d −1 over a period of 72 h, the highest value published to date for this biotransformation.