Nitrile hydratase from Rhodococcus erythropolis: Metabolization of steroidal compounds with a nitrile group
The progestin dienogest (17α-cyanomethyl-17β-hydroxy-estra-4,9-dien-3-one) was metabolized by the nitrile hydratase-containing microorganism Rhodococcus erythropolis. An enzymatic hydrolysis of the nitrile group at the 17α-side chain was intended to obtain novel derivatives and to test them for prog...
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| Veröffentlicht in: | Steroids 1999-08, Vol.64 (8), p.535-540 |
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| creator | Kaufmann, Günter Dautzenberg, Horst Henkel, Harry Müller, Gerd Schäfer, Thomas Undeutsch, Bernd Oettel, Michael |
| description | The progestin dienogest (17α-cyanomethyl-17β-hydroxy-estra-4,9-dien-3-one) was metabolized by the nitrile hydratase-containing microorganism
Rhodococcus erythropolis. An enzymatic hydrolysis of the nitrile group at the 17α-side chain was intended to obtain novel derivatives and to test them for progesterone receptor affinity. In contrast to the rapid enzymatic hydrolysis of nonsteroidal nitriles, the nitrile group of dienogest was cleaved very slowly. The dominant reaction was an aromatization of ring A. After prolonged fermentation, the 17α-acetamido derivatives of estradiol and of 9(11)-dehydroestradiol were formed. Three of the metabolites were also prepared synthetically. They were tested for hormonal activity by assessing their binding to progesterone and estrogen receptors in vitro. Neither the aromatized 17α-acetamido derivatives nor the dienogest derivative 17α-acetamido-17β-hydroxy-estra-4,9-dien-3-one, which was prepared synthetically only, exhibited affinity for the progesterone receptor. |
| doi_str_mv | 10.1016/S0039-128X(99)00028-8 |
| format | Article |
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Neither the aromatized 17α-acetamido derivatives nor the dienogest derivative 17α-acetamido-17β-hydroxy-estra-4,9-dien-3-one, which was prepared synthetically only, exhibited affinity for the progesterone receptor.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Biotransformation</subject><subject>Drug Evaluation, Preclinical</subject><subject>Estradiol - metabolism</subject><subject>Fermentation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Health. Pharmaceutical industry</subject><subject>Hormones. Growth factors</subject><subject>Hydro-Lyases - metabolism</subject><subject>Hydrolysis</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Microbial transformation</subject><subject>Nandrolone - analogs & derivatives</subject><subject>Nandrolone - chemistry</subject><subject>Nandrolone - metabolism</subject><subject>Nitrile hydratase</subject><subject>Production of active biomolecules</subject><subject>Progesterone - metabolism</subject><subject>Progesterone receptor</subject><subject>Progestin</subject><subject>Pyridines - metabolism</subject><subject>Rabbits</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Rhodococcus - metabolism</subject><subject>Steroid aromatization</subject><subject>Structure-Activity Relationship</subject><issn>0039-128X</issn><issn>1878-5867</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EYpfSn9DKhwrBIWDHm9jupUIVX1IBCYrEzZrYk67bJE5tB7T8erLdVemN08zhed8ZPYQccfaaM16_-c6Y0AUv1c-XWr9ijJWqUI_IkiupikrV8jFZ3iML8iyl6xmqhS6fkgVnKy0qrZfk5ovP0XdI1xsXIUNC2sbQ02_r4IIN1k6JYtzkdQxj6Hw6pZ8xQzOvfyD7MNDQ0pQxBu-gozb0Y5gGl-hvn9cU6LBvv4phGp-TJy10CQ_384D8eP_u8vxjcfH1w6fztxeFFZrlouGOK-B1qVwlRCOZqhslQVleIzJeVs0KrHOygdJxyQVDZ53kGhtQwikmDsiLXe8Yw-2EKZveJ4tdBwOGKRnJWLUVNoPVDrQxpBSxNWP0PcSN4cxsLZs7y2ar0Ght7iwbNeeO9wempkf3ILXTOgMnewCSha6NMFif_nG6FrLc9pztMJxt_PIYTbIeB4vOR7TZuOD_88lfQ9ecKA</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Kaufmann, Günter</creator><creator>Dautzenberg, Horst</creator><creator>Henkel, Harry</creator><creator>Müller, Gerd</creator><creator>Schäfer, Thomas</creator><creator>Undeutsch, Bernd</creator><creator>Oettel, Michael</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19990801</creationdate><title>Nitrile hydratase from Rhodococcus erythropolis: Metabolization of steroidal compounds with a nitrile group</title><author>Kaufmann, Günter ; Dautzenberg, Horst ; Henkel, Harry ; Müller, Gerd ; Schäfer, Thomas ; Undeutsch, Bernd ; Oettel, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-b1d18a1628d533b7086b87a8c16ee0125b4acdd7ba2d17130edcd719eba83d803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Biotransformation</topic><topic>Drug Evaluation, Preclinical</topic><topic>Estradiol - metabolism</topic><topic>Fermentation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Health. Pharmaceutical industry</topic><topic>Hormones. Growth factors</topic><topic>Hydro-Lyases - metabolism</topic><topic>Hydrolysis</topic><topic>Industrial applications and implications. 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Rhodococcus erythropolis. An enzymatic hydrolysis of the nitrile group at the 17α-side chain was intended to obtain novel derivatives and to test them for progesterone receptor affinity. In contrast to the rapid enzymatic hydrolysis of nonsteroidal nitriles, the nitrile group of dienogest was cleaved very slowly. The dominant reaction was an aromatization of ring A. After prolonged fermentation, the 17α-acetamido derivatives of estradiol and of 9(11)-dehydroestradiol were formed. Three of the metabolites were also prepared synthetically. They were tested for hormonal activity by assessing their binding to progesterone and estrogen receptors in vitro. Neither the aromatized 17α-acetamido derivatives nor the dienogest derivative 17α-acetamido-17β-hydroxy-estra-4,9-dien-3-one, which was prepared synthetically only, exhibited affinity for the progesterone receptor.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10493599</pmid><doi>10.1016/S0039-128X(99)00028-8</doi><tpages>6</tpages></addata></record> |
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| ispartof | Steroids, 1999-08, Vol.64 (8), p.535-540 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Biological and medical sciences Biotechnology Biotransformation Drug Evaluation, Preclinical Estradiol - metabolism Fermentation Fundamental and applied biological sciences. Psychology Health. Pharmaceutical industry Hormones. Growth factors Hydro-Lyases - metabolism Hydrolysis Industrial applications and implications. Economical aspects Microbial transformation Nandrolone - analogs & derivatives Nandrolone - chemistry Nandrolone - metabolism Nitrile hydratase Production of active biomolecules Progesterone - metabolism Progesterone receptor Progestin Pyridines - metabolism Rabbits Receptors, Estrogen - metabolism Rhodococcus - metabolism Steroid aromatization Structure-Activity Relationship |
| title | Nitrile hydratase from Rhodococcus erythropolis: Metabolization of steroidal compounds with a nitrile group |
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