Steroid transforming enzymes from microorganisms: The reverse reaction of the steroid-1-dehydrogenase from Nocardia

Groh, H.; Komel, Radovan; Deppmeyer, V.; Schade, Wolfgang; Hörhold, C.

doi:10.1016/0022-4731(80)90052-7

Cited by 16 publications

(3 citation statements)

References 6 publications

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“…A similar but not identical effect was previously described for KstD from N. opaca IMET 7030 [ 23 ] and N. corallina [ 10 ]. There, the transhydrogenation in D 2 O was conducted between progesterone and ADD in the pD range of 7.4–9.0.…”

Section: Resultssupporting

confidence: 79%

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1,2-Hydrogenation and Transhydrogenation Catalyzed by 3-Ketosteroid Δ1-Dehydrogenase from Sterolibacterium denitrificans—Kinetics, Isotope Labelling and QM:MM Modelling Studies

Wojtkiewicz

Glanowski

Waligórski

et al. 2022

IJMS

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Bacteria and fungi that are able to metabolize steroids express 3-ketosteroid-Δ1-dehydrogenases (KstDs). KstDs such as AcmB form Sterolibacterium denitrificans Chol-1 catalyze the enantioselective 1α,2β-dehydrogenation of steroids to their desaturated analogues, e.g., the formation of 1,4-androstadiene-3,17-dione (ADD) from 4-androsten-3,17-dione (AD). The reaction catalyzed by KstD can be reversed if the appropriate electron donor, such as benzyl viologen radical cation, is present. Furthermore, KstDs can also catalyze transhydrogenation, which is the transfer of H atoms between 3-ketosteroids and 1-dehydrosteroids. In this paper, we showed that AcmB exhibits lower pH optima for hydrogenation and dehydrogenation by 3.5–4 pH units than those observed for KstD from Nocardia corallina. We confirmed the enantiospecificity of 1α,2β-hydrogenation and 1α,2β-transhydrogenation catalyzed by AcmB and showed that, under acidic pH conditions, deuterons are introduced not only at 2β but also at the 1α position. We observed a higher degree of H/D exchange at Y363, which activates the C2-H bond, compared to that at FAD, which is responsible for redox at the C1 position. Furthermore, for the first time, we observed the introduction of the third deuteron into the steroid core. This effect was explained through a combination of LC-MS experiments and QM:MM modelling, and we attribute it to a decrease in the enantioselectivity of C2-H activation upon the deuteration of the 2β position. The increase in the activation barrier resulting from isotopic substitution increases the chance of the formation of d3-substituted 3-ketosteroids. Finally, we demonstrate a method for the synthesis of 3-ketosteroids chirally deuterated at 1α,2β positions, obtaining 1α,2β-d2-4-androsten-3,17-dione with a 51% yield (8.61 mg).

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Section: Resultssupporting

confidence: 79%

“…This frequently results in the unselective reduction of both the C=C and C=O bonds in steroids [ 21 , 22 ]. Therefore, applying isolated enzymes (or recombinant whole-cell systems) with recognized regio- and stereoselectivity seems to be the best approach [ 10 , 23 ].…”

Section: Resultsmentioning

confidence: 99%

1,2-Hydrogenation and Transhydrogenation Catalyzed by 3-Ketosteroid Δ1-Dehydrogenase from Sterolibacterium denitrificans—Kinetics, Isotope Labelling and QM:MM Modelling Studies

Wojtkiewicz

Glanowski

Waligórski

et al. 2022

IJMS

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“…erythropolis IMET 7 185, and M. smegmatis IMET SG 99, dehydrogenation and hydrogenation were shown to be performed by only a single enzyme. [119][120][121] Although significant amounts of the unwanted products were described to be formed during fermentation in unfavorable media and in conditions of inadequate aeration,",' I 2 . ' l 4 side-product formation in commercial 1-dehydrogenation is not as important a problem as in 11 Por 16a-hydroxylations, and in properly controlled fermentations, a product of 90% yield is not uncommon.…”

Section: -Dehydrogenationmentioning

confidence: 99%

Biotransformations of Steroids

Sedlaczek

1988

Critical Reviews in Biotechnology

114

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Different types of microbiological transformation of steroids are reviewed, with special attention given to bioconversions applied in the manufacturing of steroid hormones, i.e., 11 alpha- 11 beta-, 16 alpha-, 17 alpha-hydroxylations and 1-dehydrogenation. Availability and utilization of raw materials for industrial production of steroids of the estrane, androstane, and pregnane series are discussed. Among the current trends in steroid research of a practical nature, immobilization of enzymes and living cells and the spore process are emphasized as alternative techniques of steroid transformation of possible future importance. Efforts to recognize, in cell-free preparations, the components of steroid-transforming enzyme systems as well as the cellular mechanisms of control of their biosynthesis and activity are described in order to illustrate the main subjects of current basic investigation in steroid bioconversion.

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Steroidumwandlung mit immobilisierten Mikroorganismen

Atrat

1982

J of Basic Microbiology

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The application of immobilized microbial cells has been receiving increasing interest, in particular because of their potential for use in industrial fermentation processes and in analytical procedures. Since the first application of an immobilized microbial biocatalyst for steroid transformation in 1970 by MOSBACH and LARSSON many results have been published concerning the use of surh type of biocatalyst in steroid biochemistry and steroid microbiology, respectively. The review deals with the present scientific state of the steroid transformations performed with immobilized biocatalysts, their applications and development trends. I n particulary the following aspects are discussed: 1(2)-dehydrogenation or hydrogenation, hydroxylation reactions, redox processes in 3,17-and 20-oxogroups, side chain splitting of sterols, 5a-reduction, modification of cholic acid derivatives and the use of immobilized plant cells. The possibility for application of microbial membrane electrodes in steroid analysis has been shown. Up to now, many results of fundamental research are known. There are possibilities for producing expensive steroid derivatives in laboratory apparatures using immobilized biocatalysts. Some of the processes, described here, are of practical interest, and some of them are said to be used industrially, respectiveiy.

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Steroid transforming enzymes from microorganisms: The reverse reaction of the steroid-1-dehydrogenase from Nocardia

Cited by 16 publications

References 6 publications

1,2-Hydrogenation and Transhydrogenation Catalyzed by 3-Ketosteroid Δ1-Dehydrogenase from Sterolibacterium denitrificans—Kinetics, Isotope Labelling and QM:MM Modelling Studies

1,2-Hydrogenation and Transhydrogenation Catalyzed by 3-Ketosteroid Δ1-Dehydrogenase from Sterolibacterium denitrificans—Kinetics, Isotope Labelling and QM:MM Modelling Studies

Biotransformations of Steroids

Steroidumwandlung mit immobilisierten Mikroorganismen

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