Transformation of a series of saturated isomeric steroidal diols by Aspergillus tamarii KITA reveals a precise stereochemical requirement for entrance into the lactonization pathway

Hunter, A. Christy; Collins, Catherine A.; Dodd, Howard T.; Dedi, Cinzia; Koussoroplis, Salome Juliette

doi:10.1016/j.jsbmb.2010.08.010

Cited by 12 publications

(6 citation statements)

References 38 publications

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“…Oxidation of the 3β-OH group was fully supported by the loss of a methine signal at δ c 71.5 ppm in the starting material 13 C-NMR spectrum, being replaced by a new non-protonated resonance signal in the product spectrum at δ c 199.4 ppm. All these observations for metabolites 5 – 8 were in agreement with those reported in the literature [6,17,18,30].…”

Section: Resultssupporting

confidence: 92%

“…1 H-NMR δ (ppm): 0.73 (3H, s, 19-CH 3 ), 1.28 (3H, s, 18-CH 3 ), 4.05 (1H, t, J = 2.7 Hz, 3β-H), 13 C-NMR δ (ppm): 172.0 (C-17), 83.4 (C-13), 66.2 (C-3), 53.0 (C-9), 46.3 (C-14), 39.3 (C-12), 38.4 (C-5), 37.9 (C-8), 36.0 (C-10), 35.5 (C-4), 31.9 (C-1), 30.5 (C-7), 28.9 (C-2), 28.6 (C-16), 28.1 (C-6), 21.5 (C-11), 20.1 (C-18), 19.6 (C-15), 11.0 (C-19). The spectroscopic data corresponded to those described in literature [17].…”

Section: Methodssupporting

confidence: 74%

“…The use of the chimeric enzyme PASTMO (a hybrid of phenylacetone monooxygenase (PAMO) and bacterial steroid monooxygenase (STMO) from Rhodococcus rhodochrous ) in the biotransformation of progesterone afforded the final lactone (testololactone) with a moderate (19%) conversion [4]. Among microorganisms, fungal species of the Penicillium [5,6,7,8,9,10], Aspergillus [11,12,13,14,15,16,17,18,19,20] and Fusarium genera [21,22,23] are especially known to transform 4-en-3-oxo and 3β-hydroxy-5-ene C 21 as well as C 19 steroids. Enzymes performing oxidation belong to the family of NADPH-dependent steroid Baeyer-Villiger monooxygenases (BVMOs) containing FAD as a cofactor.…”

Section: Introductionmentioning

confidence: 99%

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Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum

Świzdor

2013

Molecules

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Abstract:The biotransformation of androsterone (1), epiandrosterone (2), androstanedione (3) and DHEA (dehydroepiandrosterone) (4) by Penicillium lanosocoeruleum-a fungal species not used in biotransformations so far-were described. All the substrates were converted in high yield (70%-99%) into D ring δ-lactones. The oxidation of 1 produced 3α-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (5). The oxidation of 2 led to 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (6). The biotransformation of 3 resulted in the formation of 3α-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (5) and 17a-oxa-Dhomo-5α-androstan-3,17-dione (7). An analysis of the transformation progress of the studied substrates as a function of time indicates that the Baeyer-Villiger monooxygenase of this fungus does not accept the 3β-hydroxy-5-ene functionality of steroids. In this microorganism steroidal 3β-hydroxy-dehydrogenase (3β-HSD) was active, and as a result DHEA (4) was transformed exclusively to testololactone (8). Apart from the observed oxidative transformations, a reductive pathway was revealed with the C-3 ketone being reduced to a C-3α-alcohol. It is demonstrated for the first time that the reduction of the 3-keto group of the steroid nucleus can occur in the presence of a ring-D lactone functionality.

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Section: Resultssupporting

confidence: 92%

Section: Methodssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum

Świzdor

2013

Molecules

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“…This result provides strong support for the “one enzyme, multiple substrate orientations” hypothesis. Stereochemical restrictions were also invoked to rationalize the diverse metabolites of steroids in cultures of Aspergillus tamarii [ 11 – 13 ]. Our studies indicated that this mechanism may also occur in steroid hydroxylation reactions carried out by cultures of the filamentous fungi Beauveria bassiana , Absidia coerulea , and Mortierella isabellina [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Insight into the orientational versatility of steroid substrates—a docking and molecular dynamics study of a steroid receptor and steroid monooxygenase

et al. 2017

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Numerous steroids are essential plant, animal, and human hormones. The medical and industrial applications of these hormones require the identification of new synthetic routes, including biotransformations. The metabolic fate of a steroid can be complicated; it may be transformed into a variety of substituted derivatives. This may be because a steroid molecule can adopt several possible orientations in the binding pocket of a receptor or an enzyme. The present study, based on docking and molecular dynamics, shows that it is indeed possible for a steroid molecule to bind to a receptor binding site in two or more orientations (normal, head-to-tail reversed, upside down). Three steroids were considered: progesterone, dehydroepiandrosterone, and 7-oxo-dehydroepiandrosterone. Two proteins were employed as hosts: the human mineralocorticoid receptor and a bacterial Baeyer–Villiger monooxygenase. When the steroids were in nonstandard orientations, the estimated binding strength was found to be only moderately diminished and the network of hydrogen bonds between the steroid and the host was preserved.

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“…As far as biotransformations by A. tamarii are concerned, A. tamarii QM 1223 has been the only strain of this fungus used for steroid biotransformation [17][18][19][20][21][22][23][24][25] . This strain mainly showed BVMO activities on different steroidal substrates and has attracted considerable interest due to its ability to transform progesterone (4) into testolactone (9) in high yield.…”

mentioning

confidence: 99%

Baeyer–Villiger oxidation of some steroids by Aspergillus tamarii MRC 72400

Yildirim

Uzuner

Gulcuoglu

2011

Collect. Czech. Chem. Commun.

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Biotransformations of epiandrosterone (1), dehydroepiandrosterone (2), testosterone (3), progesterone (4) and pregnenolone (5) by Aspergillus tamarii MRC 72400 for 5 days have been reported and the results of these incubations have been compared with previously published data obtained with Aspergillus tamarii QM 1223. A. tamarii MRC 72400 showed higher Bayer-Villiger monooxygenase activities than A. tamarii QM 1223 did. Apart from pregnenolone (5), A. tamarii MRC 72400 metabolized these steroids in different ways. Incubation of epiandrosterone (1) afforded 3β,11β-dihydroxy-5α-androstan-17-one (6) (3%) and 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (7) (9.5%). Incubation of dehydroepiandrosterone (2) afforded 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one (8) (28%), testolactone (9) (6%), 3β,7β-dihydroxyandrost-5-en-17-one (10) (13%) and 3β,7α-dihydroxyandrost-5-en-17-one (11) (24%). Incubation of testosterone (3) afforded testolactone (9) (58%). Incubation of progesterone (4) also afforded testolactone (9), however in higher yield (86%). Incubation of pregnenolone (5) afforded 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one (8) (25%) and testolactone (9) (27%).A number of investigations involving microbial biotransformations of a wide range of steroidal substrates have been carried out due to their potential for the preparation of more valuable and functionalized compounds such as steroid drugs and hormones 1-3 . There are still enormous efforts to increase the efficiency of microbial steroid biotransformations and to find new useful microorganisms and reactions 1 . For example, some of these steroid biotransformations have been carried out using Aspergillus wentii 4 , Penicillium digitatum 5 and Aspergillus terreus 6 . A. wentii showed some high hydroxylase activities whereas P. digitatum and A. terreus showed some low 5α-reductase and Baeyer-Villiger monooxygenase (BVMO) activities, respectively.

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Transformation of a series of saturated isomeric steroidal diols by Aspergillus tamarii KITA reveals a precise stereochemical requirement for entrance into the lactonization pathway

Cited by 12 publications

References 38 publications

Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum

Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum

Insight into the orientational versatility of steroid substrates—a docking and molecular dynamics study of a steroid receptor and steroid monooxygenase

Baeyer–Villiger oxidation of some steroids by Aspergillus tamarii MRC 72400

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