The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Shridhar Patil - One of the best experts on this subject based on the ideXlab platform.
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Parameter optimization for progesterone to 17 -ketosteroids bioconversion by co-culture of Pseudomonas diminuta and Delftia acidovorans
2014Co-Authors: Tushar Banerjee, Pushpendra Awadhiya, Shridhar PatilAbstract:Progesterone is an important precursor for the production of androst-4-ene-3, 17-dione (AD) by C-17 side chain cleavage and Androsta-1, 4-diene-3, 17-dione (ADD) by side-chain cleavage and -dehydrogenation reaction (Manosroi et al., 2008). Progesterone is available in large quantities through chemical degradation of steroidal alkaloids and sapogenins (Asolkar and Chadha, 1979).The production of male and female sex hormones form progesterone through chemical route requires its conversion to two key 17-ketosteroids, AD and ADD respectively (Martin, 1977). Female hormones (Estrogen and analogous) are the major steroid hormones produced worldwide using AD and ADD. Estrogen replacement therapy is a major tool to combat postmenopausal osteoporosis in women (Neunzehn, J. et al., 2014), which employs estrogen from external sources. The side chain cleavage (Lin et al., 2009) and dehydrogenation activities are widely distributed in several microorganisms (Gharaei-Fathabad, and Chabra 2011; Manosroi et al., 2008). The bioconversion pathway of 16-DPA to ADD by a mixed culture of Pseudomonas diminuta MTCC ISSN: 2319-7706 Volume 3 Number 8 (2014) pp. 793-801 http://www.ijcmas.com
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mixed culture bioconversion of 16 dehydropregnenolone acetate to Androsta 1 4 diene 3 17 dione optimization of parameters
Biotechnology Progress, 2003Co-Authors: Tushar Banerjee, Aniruddha Shukla, Kirti Shinde, Shridhar PatilAbstract:Bioconversion of 16-dehydropregnenolone acetate (16-DPA) to Androsta-1,4-diene-3,17-dione (ADD), an intermediate for the production of female sex hormones, by mixed culture of Pseudomonas diminuta MTCC 3361 and Comamonas acidovorans MTCC 3362 is reported. Various physicochemical parameters for the bioconversion of 16-DPA to ADD have been optimized in shake flask cultures. Nutrient broth inoculated with actively growing co-culture proved ideal for bacterial growth and bioconversion. A temperature range of 35-40 degrees C was most suitable; higher or lower temperatures adversely affected the bioconversion. Dimethylformamide below 2% concentration was the most suitable carrier solvent. Maximum conversion was recorded at 0.5 mg mL(-1) 16-DPA. A pH of 5.0 yielded a peak conversion of 62 mol % in 120 h incubation period. Addition of 9alpha-hydroxylase inhibitors failed to prevent further breakdown of ADD to nonsteroidal products. 16-DPA conversion in a 5 L fermenter followed a similar trend.
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bioconversion of 3β acetoxypregna 5 16 diene 20 one to Androsta 1 4 diene 3 17 dione by mixed bacterial culture
Letters in Applied Microbiology, 2002Co-Authors: Shridhar Patil, Kirti Shinde, Aniruddha Shukla, Tushar BanerjeeAbstract:Aims: To isolate a bacterium capable of degrading 3β-acetoxypregna-5,16-diene-20-one (16-DPA) to Androsta-1,4-diene-3,17-dione (ADD) and to decipher the biodegradation pathway. Methods and Results: Isolation on mineral salt agar containing 16-DPA as sole carbon source yielded two bacteria identified as Pseudomonas diminuta and Comamonas acidovorons. These bacteria failed to degrade 16-DPA individually in pure cultures but converted 16-DPA to ADD in a mixed culture. The intermediates accumulated during the bioconversion were identified as pregna-4,16-diene-3,20-dione and pregna-1,4,16-triene-3,20-dione. Conclusions: The degradation pattern of 16-DPA by mixed bacterial culture revealed the reaction sequence as (i) cleavage of C-3 acetyl function, (ii) dehydrogenation at C-1 and C-2 positions and (iii) cleavage of C-17 side-chain. Significance and Impact of the Study: The present work opens a new approach towards the production of a female sex hormone precursor and elucidates the biodegradation pathway of 16-DPA by mixed bacterial culture.
Tushar Banerjee - One of the best experts on this subject based on the ideXlab platform.
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Parameter optimization for progesterone to 17 -ketosteroids bioconversion by co-culture of Pseudomonas diminuta and Delftia acidovorans
2014Co-Authors: Tushar Banerjee, Pushpendra Awadhiya, Shridhar PatilAbstract:Progesterone is an important precursor for the production of androst-4-ene-3, 17-dione (AD) by C-17 side chain cleavage and Androsta-1, 4-diene-3, 17-dione (ADD) by side-chain cleavage and -dehydrogenation reaction (Manosroi et al., 2008). Progesterone is available in large quantities through chemical degradation of steroidal alkaloids and sapogenins (Asolkar and Chadha, 1979).The production of male and female sex hormones form progesterone through chemical route requires its conversion to two key 17-ketosteroids, AD and ADD respectively (Martin, 1977). Female hormones (Estrogen and analogous) are the major steroid hormones produced worldwide using AD and ADD. Estrogen replacement therapy is a major tool to combat postmenopausal osteoporosis in women (Neunzehn, J. et al., 2014), which employs estrogen from external sources. The side chain cleavage (Lin et al., 2009) and dehydrogenation activities are widely distributed in several microorganisms (Gharaei-Fathabad, and Chabra 2011; Manosroi et al., 2008). The bioconversion pathway of 16-DPA to ADD by a mixed culture of Pseudomonas diminuta MTCC ISSN: 2319-7706 Volume 3 Number 8 (2014) pp. 793-801 http://www.ijcmas.com
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mixed culture bioconversion of 16 dehydropregnenolone acetate to Androsta 1 4 diene 3 17 dione optimization of parameters
Biotechnology Progress, 2003Co-Authors: Tushar Banerjee, Aniruddha Shukla, Kirti Shinde, Shridhar PatilAbstract:Bioconversion of 16-dehydropregnenolone acetate (16-DPA) to Androsta-1,4-diene-3,17-dione (ADD), an intermediate for the production of female sex hormones, by mixed culture of Pseudomonas diminuta MTCC 3361 and Comamonas acidovorans MTCC 3362 is reported. Various physicochemical parameters for the bioconversion of 16-DPA to ADD have been optimized in shake flask cultures. Nutrient broth inoculated with actively growing co-culture proved ideal for bacterial growth and bioconversion. A temperature range of 35-40 degrees C was most suitable; higher or lower temperatures adversely affected the bioconversion. Dimethylformamide below 2% concentration was the most suitable carrier solvent. Maximum conversion was recorded at 0.5 mg mL(-1) 16-DPA. A pH of 5.0 yielded a peak conversion of 62 mol % in 120 h incubation period. Addition of 9alpha-hydroxylase inhibitors failed to prevent further breakdown of ADD to nonsteroidal products. 16-DPA conversion in a 5 L fermenter followed a similar trend.
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bioconversion of 3β acetoxypregna 5 16 diene 20 one to Androsta 1 4 diene 3 17 dione by mixed bacterial culture
Letters in Applied Microbiology, 2002Co-Authors: Shridhar Patil, Kirti Shinde, Aniruddha Shukla, Tushar BanerjeeAbstract:Aims: To isolate a bacterium capable of degrading 3β-acetoxypregna-5,16-diene-20-one (16-DPA) to Androsta-1,4-diene-3,17-dione (ADD) and to decipher the biodegradation pathway. Methods and Results: Isolation on mineral salt agar containing 16-DPA as sole carbon source yielded two bacteria identified as Pseudomonas diminuta and Comamonas acidovorons. These bacteria failed to degrade 16-DPA individually in pure cultures but converted 16-DPA to ADD in a mixed culture. The intermediates accumulated during the bioconversion were identified as pregna-4,16-diene-3,20-dione and pregna-1,4,16-triene-3,20-dione. Conclusions: The degradation pattern of 16-DPA by mixed bacterial culture revealed the reaction sequence as (i) cleavage of C-3 acetyl function, (ii) dehydrogenation at C-1 and C-2 positions and (iii) cleavage of C-17 side-chain. Significance and Impact of the Study: The present work opens a new approach towards the production of a female sex hormone precursor and elucidates the biodegradation pathway of 16-DPA by mixed bacterial culture.
Mitsuteru Numazawa - One of the best experts on this subject based on the ideXlab platform.
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probing the binding pocket of the active site of aromatase with 2 phenylaliphatic Androsta 1 4 diene 3 17 dione steroids
Steroids, 2010Co-Authors: Madoka Takahashi, Kouwa Yamashita, Mitsuteru NumazawaAbstract:Abstract A series of 2-phenylaliphatic-substituted Androsta-1,4-diene-3,17-diones (6) as well as their androstenedione derivatives (5) were synthesized as aromatase inhibitors to gain insights of structure–activity relationships of varying the alkyl moiety (C1 to C4) of the 2-phenylaliphatic substituents as well as introducing a methyl- or trifluoromethyl function to p-position of a phenethyl moiety to the inhibitory activity. The inhibitors examined showed a competitive type inhibition. The 2-phenpropylAndrosta-1,4-diene 6c was the most powerful inhibitor (Ki: 16.1 nM) among them. Compounds 6c along with the phenethyl derivative 6b caused a time-dependent inactivation of aromatase (kinact: 0.0293 and 0.0454 min−1 for 6b and 6c, respectively). The inactivation was prevented by the substrate androstenedione, and no significant effect of l -cysteine on the inactivation was observed in each case. Molecular docking of the phenpropyl compound 6c to aromatase was conducted to demonstrate that the phenpropyl group orients to a hydrophobic binding pocket in the active site to result in the formation of thermodynamically stable enzyme–inhibitor complex.
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aromatase inactivation by 2 substituted derivatives of the suicide substrate Androsta 1 4 diene 3 17 dione
The Journal of Steroid Biochemistry and Molecular Biology, 2009Co-Authors: Madoka Takahashi, Wakako Handa, Hiromi Umeta, Saki Ishikawa, Kouwa Yamashita, Mitsuteru NumazawaAbstract:To gain the structure-activity relationship of Delta(1)-androstenediones (Delta(1)-ADs) as mechanism-based inactivator of aromatase, series of 2-alkyl- and 2-alkoxy-substituted Delta(1)-ADs (6 and 9) as well as 2-bromo-Delta(1)-AD (14) were synthesized and tested. All of the inhibitors examined blocked aromatase in human placental microsomes in a competitive manner. In a series of 2-alkyl-Delta(1)-ADs (6), n-hexyl compound 6f was the most powerful inhibitor with an apparent K(i) value of 31 nM. The inhibitory activities of 2-alkoxy steroids 9 decreased in relation to length of the alkyl chain up to n-hexyloxy group (K(i): 95 nM for methoxy 9a). All of the alkyl steroids 6 along with the alkoxy steroid 9, except for the ethyl and n-propyl compounds 6b and 6c, caused a time-dependent inactivation of aromatase. The inactivation rates (k(inact): 0.020-0.084 min(-1)) were comparable to that of the parent compound Delta(1)-AD. The inactivation was prevented by the substrate AD, and no significant effect of l-cysteine on the inactivation was observed in each case. The results indicate that the 2-hexyl compound 6f act as the most powerful mechanism-based inactivator of aromatase among Delta(1)-AD analogs and may be submitted to the preclinical study in estrogen-dependent breast cancer.
Muhammad Iqbal Choudhary - One of the best experts on this subject based on the ideXlab platform.
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SOLID PHASE MICROBIAL FERMENTATION OF ANABOLIC STEROID, DIHYDROTESTOSTERONE WITH ASCOMYCETE FUNGUS FUSARIUM OXYSPORUM
International Journal of Pharmacy and Pharmaceutical Sciences, 2015Co-Authors: Muhammad Atif, Syed Adnan Ali Shah, Sadia Sultan, Muhammad Iqbal ChoudharyAbstract:Objective: Microbial catalysis is used in the commercial production of many bioactive steroids. Solid phase microbial fermentation of anabolic steroid, dihydrotestosterone (DHT, 1 ), was carried out with ascomycete fungal strain Fusarium oxysporum (NRRL-1392). Methods: Sabouraud-4% glucose-agar was used to cultivate the fungal cultures as solid phase medium. Substrate 1 was incubated with Fusarium oxysporum (NRRL-1392) for 8 days. Microbial transformed metabolites were purified by using column chromatographic technique. Results: Ascomycete fungal strain Fusarium oxysporum (NRRL-1392), transformed dihydrotestosterone ( 1 ) to four oxidative metabolites 2-5 using solid phase microbial transformation metod. During biotransformation process the hydroxy group was incorporated in inactivated methine carbon atoms at C-7 and C-11 positions. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques as 17b-hydroxyAndrosta-1, 4-dien-3-one 2 , Androsta-1, 4-diene-3, 17-dione 3 , 7a, 17b-dihydroxyAndrosta-1, 4-dien-3-one ( 4 ), and 11a-hydroxyAndrosta-1, 4-diene-3, 17-dione 5 . The relative stereochemistry of newly incorporated hydroxy groups were deduced by 2D NOESY experiment. Conclusion: In conclusion, microbial biocatalysis is an attractive alternative tool for the preparation of new bioactive steroids, which might be difficult to prepare by conventional chemical routes. Furthermore, microbial-catalyzed biotransformations can produce commercially valuable steroidal pharmaceuticals for the pharmaceutical industry.
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SOLID PHASE MICROBIAL FERMENTATION OF ANABOLIC STEROID, DIHYDROTESTOSTERONE WITH ASCOMYCETE FUNGUS FUSARIUM OXYSPORUM Original Article
2015Co-Authors: Muhammad Atif, Syed Adnan Ali Shah, Sadia Sultan, Muhammad Iqbal Choudhary, Selangor Darul EhsanAbstract:Objective: Microbial catalysis is used in the commercial production of many bioactive steroids. Solid phase microbial fermentation of anabolic steroid, dihydrotestosterone (DHT, 1), was carried out with ascomycete fungal strain Fusarium oxysporum (NRRL-1392). Methods: Sabouraud-4% glucose-agar was used to cultivate the fungal cultures as solid phase medium. Substrate 1 was incubated with Fusarium oxysporum (NRRL-1392) for 8 days. Microbial transformed metabolites were purified by using column chromatographic technique. Results: Ascomycete fungal strain Fusarium oxysporum (NRRL-1392), transformed dihydrotestosterone (1) to four oxidative metabolites 2-5 using solid phase microbial transformation metod. During biotransformation process the hydroxy group was incorporated in inactivated methine carbon atoms at C-7 and C-11 positions. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques as 17βhydroxyAndrosta-1, 4-dien-3-one 2, Androsta-1, 4-diene-3, 17-dione 3, 7α, 17β-dihydroxyAndrosta-1, 4-dien-3-one (4), and 11α-hydroxyAndrosta-1, 4diene-3, 17-dione 5. The relative stereochemistry of newly incorporated hydroxy groups were deduced by 2D NOESY experiment. Conclusion: In conclusion, microbial biocatalysis is an attractive alternative tool for the preparation of new bioactive steroids, which might be difficult to prepare by conventional chemical routes. Furthermore, microbial-catalyzed biotransformations can produce commercially valuable steroidal pharmaceuticals for the pharmaceutical industry.
Muhammad Atif - One of the best experts on this subject based on the ideXlab platform.
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SOLID PHASE MICROBIAL FERMENTATION OF ANABOLIC STEROID, DIHYDROTESTOSTERONE WITH ASCOMYCETE FUNGUS FUSARIUM OXYSPORUM
International Journal of Pharmacy and Pharmaceutical Sciences, 2015Co-Authors: Muhammad Atif, Syed Adnan Ali Shah, Sadia Sultan, Muhammad Iqbal ChoudharyAbstract:Objective: Microbial catalysis is used in the commercial production of many bioactive steroids. Solid phase microbial fermentation of anabolic steroid, dihydrotestosterone (DHT, 1 ), was carried out with ascomycete fungal strain Fusarium oxysporum (NRRL-1392). Methods: Sabouraud-4% glucose-agar was used to cultivate the fungal cultures as solid phase medium. Substrate 1 was incubated with Fusarium oxysporum (NRRL-1392) for 8 days. Microbial transformed metabolites were purified by using column chromatographic technique. Results: Ascomycete fungal strain Fusarium oxysporum (NRRL-1392), transformed dihydrotestosterone ( 1 ) to four oxidative metabolites 2-5 using solid phase microbial transformation metod. During biotransformation process the hydroxy group was incorporated in inactivated methine carbon atoms at C-7 and C-11 positions. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques as 17b-hydroxyAndrosta-1, 4-dien-3-one 2 , Androsta-1, 4-diene-3, 17-dione 3 , 7a, 17b-dihydroxyAndrosta-1, 4-dien-3-one ( 4 ), and 11a-hydroxyAndrosta-1, 4-diene-3, 17-dione 5 . The relative stereochemistry of newly incorporated hydroxy groups were deduced by 2D NOESY experiment. Conclusion: In conclusion, microbial biocatalysis is an attractive alternative tool for the preparation of new bioactive steroids, which might be difficult to prepare by conventional chemical routes. Furthermore, microbial-catalyzed biotransformations can produce commercially valuable steroidal pharmaceuticals for the pharmaceutical industry.
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SOLID PHASE MICROBIAL FERMENTATION OF ANABOLIC STEROID, DIHYDROTESTOSTERONE WITH ASCOMYCETE FUNGUS FUSARIUM OXYSPORUM Original Article
2015Co-Authors: Muhammad Atif, Syed Adnan Ali Shah, Sadia Sultan, Muhammad Iqbal Choudhary, Selangor Darul EhsanAbstract:Objective: Microbial catalysis is used in the commercial production of many bioactive steroids. Solid phase microbial fermentation of anabolic steroid, dihydrotestosterone (DHT, 1), was carried out with ascomycete fungal strain Fusarium oxysporum (NRRL-1392). Methods: Sabouraud-4% glucose-agar was used to cultivate the fungal cultures as solid phase medium. Substrate 1 was incubated with Fusarium oxysporum (NRRL-1392) for 8 days. Microbial transformed metabolites were purified by using column chromatographic technique. Results: Ascomycete fungal strain Fusarium oxysporum (NRRL-1392), transformed dihydrotestosterone (1) to four oxidative metabolites 2-5 using solid phase microbial transformation metod. During biotransformation process the hydroxy group was incorporated in inactivated methine carbon atoms at C-7 and C-11 positions. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques as 17βhydroxyAndrosta-1, 4-dien-3-one 2, Androsta-1, 4-diene-3, 17-dione 3, 7α, 17β-dihydroxyAndrosta-1, 4-dien-3-one (4), and 11α-hydroxyAndrosta-1, 4diene-3, 17-dione 5. The relative stereochemistry of newly incorporated hydroxy groups were deduced by 2D NOESY experiment. Conclusion: In conclusion, microbial biocatalysis is an attractive alternative tool for the preparation of new bioactive steroids, which might be difficult to prepare by conventional chemical routes. Furthermore, microbial-catalyzed biotransformations can produce commercially valuable steroidal pharmaceuticals for the pharmaceutical industry.