The Experts below are selected from a list of 477 Experts worldwide ranked by ideXlab platform
Hiromichi Minami - One of the best experts on this subject based on the ideXlab platform.
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Laboratory-scale production of (S)-reticuline, an important intermediate of benzylisoquinoline alkaloids, using a bacterial-based method.
Bioscience Biotechnology and Biochemistry, 2016Co-Authors: Eitaro Matsumura, Akira Nakagawa, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Yusuke Tomabechi, Hiromichi MinamiAbstract:Benzylisoquinoline alkaloids (BIAs) are a group of plant secondary metabolites that have been identified as targets for drug discovery because of their diverse pharmaceutical activities. Well-known BIAs are relatively abundant in plants and have therefore been extensively studied. However, although unknown BIAs are also thought to have valuable activities, they are difficult to obtain because the raw materials are present at low abundance in nature. We have previously reported the fermentative production of an important intermediate (S)-reticuline from dopamine using Escherichia coli. However, the yield is typically limited. Here, we improved production efficiency by combining in vivo Tetrahydropapaveroline production in E. coli with in vitro enzymatic synthesis of (S)-reticuline. Finally, 593 mg of pure (S)-reticuline was obtained from 1 L of the reaction mixture. Because this bacterial-based method is simple, it could be widely used for production of (S)-reticuline and related BIAs, thereby facilitating...
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Laboratory-scale production of (S)-reticuline, an important intermediate of benzylisoquinoline alkaloids, using a bacterial-based method
2016Co-Authors: Eitaro Matsumura, Akira Nakagawa, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Yusuke Tomabechi, Hiromichi MinamiAbstract:Benzylisoquinoline alkaloids (BIAs) are a group of plant secondary metabolites that have been identified as targets for drug discovery because of their diverse pharmaceutical activities. Well-known BIAs are relatively abundant in plants and have therefore been extensively studied. However, although unknown BIAs are also thought to have valuable activities, they are difficult to obtain because the raw materials are present at low abundance in nature. We have previously reported the fermentative production of an important intermediate (S)-reticuline from dopamine using Escherichia coli. However, the yield is typically limited. Here, we improved production efficiency by combining in vivo Tetrahydropapaveroline production in E. coli with in vitro enzymatic synthesis of (S)-reticuline. Finally, 593 mg of pure (S)-reticuline was obtained from 1 L of the reaction mixture. Because this bacterial-based method is simple, it could be widely used for production of (S)-reticuline and related BIAs, thereby facilitating studies of BIAs for drug discovery. High amount of pure (S)-reticuline.
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r s Tetrahydropapaveroline production by stepwise fermentation using engineered escherichia coli
Scientific Reports, 2015Co-Authors: Akira Nakagawa, Chiaki Matsuzaki, Eitaro Matsumura, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Hiromichi MinamiAbstract:Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield was quite low (<5 μM), mainly because of the oxidation of THP by tyrosinase, an essential enzyme in our production system. To circumvent these problems, we constructed a stepwise (R,S)-THP production system, in which the dopamine-producing step and the subsequent THP-producing step were separated. The yield of (R,S)-THP reached 1.0 mM (287 mg/L), the highest yielding BIA production method using a microbe reported to date. Furthermore, we demonstrated that (R,S)-THP produced by stepwise fermentation is useful for the production of reticuline, an important BIAs intermediate. Based on these observations, applying the stepwise fermentation method is discussed.
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(R,S)-Tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli.
Scientific reports, 2014Co-Authors: Akira Nakagawa, Chiaki Matsuzaki, Eitaro Matsumura, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Hiromichi MinamiAbstract:Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield was quite low (
Matthias F. Melzig - One of the best experts on this subject based on the ideXlab platform.
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Alcohol induces formation of morphine precursors in the striatum of rats
Life sciences, 1997Co-Authors: Hanka Haber, Irmgard Roske, Matthias Rottmann, Monika Georgi, Matthias F. MelzigAbstract:Dopamine-derived alkaloids, the tetrahydroisoquinolines (TIQs), are suspected to play a role in the pathogenesis of alcoholism. The present study describes the alcohol induced formation of the S-enantiomer of Tetrahydropapaveroline and Norcoclaurine in the rat brain. These compounds are of special interest since both were found as being intermediates in the biosynthesis of morphine in the opium poppy. The concentration of both TIQs were determined in different brain regions of Wistar rats after 6 and 18 months alcohol consumption ad libitum. Gas chromatography/mass spectrometry was used for the detection and quantification of the enantiomers. Tetrahydropapaveroline and norcoclaurine were detected only in the striatum of those rats which had consumed alcohol for 18 month, neither in other brain regions nor in any brain regions of the controls or the short term (6 month) alcohol treated rats. These findings and the fact that those tetrahydroisoquinolines were only detected in the striatum of the alcohol fed rats and were present only as the S-enantiomers suggest that an alcohol induced biosynthetic pathway exists in the mammalian brain.
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The in Vitro Formation of 1,3-Dimethyl-1,2,3,4-Tetrahydroisoquinoline, a Neurotoxic Metabolite of Amphetamines
Alzheimer’s and Parkinson’s Diseases, 1995Co-Authors: Hanka Haber, Michael A. Collins, Matthias F. MelzigAbstract:Since the early 1970s interest has been directed towards proposals suggesting the involvement of Pictet-Spengler condensation products, the tetrahydroisoquinolines (TIQ), in the aetiology of alcohol addiction. These products might be formed following alcohol consumption by a condensation between monoamine and an aldehyde, in particular, acetaldehyde. The most studied of all Pictet-Spengler condensation products is salsolinol (1-methyl-6,7-dihydroxy1,2,3,4-tetrahydroisoquinoline), the product of a direct cyclization between dopamine and acetaldehyde. The in vivo formation of Tetrahydropapaveroline by the condensation between dopamine and its deaminated metabolite, 3,4-dihydroxyphenylacetaldehyde (dopaldehyde), has also been postulated (Figure 1).1
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A new rapid method for the analysis of catecholic tetrahydroisoquinolines from biological samples by gas chromatography/mass spectrometry.
Analytical biochemistry, 1995Co-Authors: Hanka Haber, H.m. Haber, Matthias F. MelzigAbstract:A new method for the analysis of tetrahydroisoquinolines (TIQ) from biological materials is described. The method combines extraction and acylation of the TIQs from urine in a one-step procedure followed by analysis by gas chromatography/mass spectrometry. By this extractive derivatization method, a decrease of the extraction time, to speed up sample preparation in order to minimize oxidative side reaction, has been achieved. The detection limits for the analysis of salsolinol and salsolin in urine were 10 fmol/ml sample volume. Tetrahydropapaveroline could only be detected in spiked urine samples with a detection limit of 1 pmol/ml urine. The method is not only restricted to urine samples, but can also be applied to a variety of tissue types, including blood components.
Akira Nakagawa - One of the best experts on this subject based on the ideXlab platform.
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Laboratory-scale production of (S)-reticuline, an important intermediate of benzylisoquinoline alkaloids, using a bacterial-based method.
Bioscience Biotechnology and Biochemistry, 2016Co-Authors: Eitaro Matsumura, Akira Nakagawa, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Yusuke Tomabechi, Hiromichi MinamiAbstract:Benzylisoquinoline alkaloids (BIAs) are a group of plant secondary metabolites that have been identified as targets for drug discovery because of their diverse pharmaceutical activities. Well-known BIAs are relatively abundant in plants and have therefore been extensively studied. However, although unknown BIAs are also thought to have valuable activities, they are difficult to obtain because the raw materials are present at low abundance in nature. We have previously reported the fermentative production of an important intermediate (S)-reticuline from dopamine using Escherichia coli. However, the yield is typically limited. Here, we improved production efficiency by combining in vivo Tetrahydropapaveroline production in E. coli with in vitro enzymatic synthesis of (S)-reticuline. Finally, 593 mg of pure (S)-reticuline was obtained from 1 L of the reaction mixture. Because this bacterial-based method is simple, it could be widely used for production of (S)-reticuline and related BIAs, thereby facilitating...
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Laboratory-scale production of (S)-reticuline, an important intermediate of benzylisoquinoline alkaloids, using a bacterial-based method
2016Co-Authors: Eitaro Matsumura, Akira Nakagawa, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Yusuke Tomabechi, Hiromichi MinamiAbstract:Benzylisoquinoline alkaloids (BIAs) are a group of plant secondary metabolites that have been identified as targets for drug discovery because of their diverse pharmaceutical activities. Well-known BIAs are relatively abundant in plants and have therefore been extensively studied. However, although unknown BIAs are also thought to have valuable activities, they are difficult to obtain because the raw materials are present at low abundance in nature. We have previously reported the fermentative production of an important intermediate (S)-reticuline from dopamine using Escherichia coli. However, the yield is typically limited. Here, we improved production efficiency by combining in vivo Tetrahydropapaveroline production in E. coli with in vitro enzymatic synthesis of (S)-reticuline. Finally, 593 mg of pure (S)-reticuline was obtained from 1 L of the reaction mixture. Because this bacterial-based method is simple, it could be widely used for production of (S)-reticuline and related BIAs, thereby facilitating studies of BIAs for drug discovery. High amount of pure (S)-reticuline.
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r s Tetrahydropapaveroline production by stepwise fermentation using engineered escherichia coli
Scientific Reports, 2015Co-Authors: Akira Nakagawa, Chiaki Matsuzaki, Eitaro Matsumura, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Hiromichi MinamiAbstract:Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield was quite low (<5 μM), mainly because of the oxidation of THP by tyrosinase, an essential enzyme in our production system. To circumvent these problems, we constructed a stepwise (R,S)-THP production system, in which the dopamine-producing step and the subsequent THP-producing step were separated. The yield of (R,S)-THP reached 1.0 mM (287 mg/L), the highest yielding BIA production method using a microbe reported to date. Furthermore, we demonstrated that (R,S)-THP produced by stepwise fermentation is useful for the production of reticuline, an important BIAs intermediate. Based on these observations, applying the stepwise fermentation method is discussed.
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(R,S)-Tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli.
Scientific reports, 2014Co-Authors: Akira Nakagawa, Chiaki Matsuzaki, Eitaro Matsumura, Takashi Koyanagi, Takane Katayama, Kenji Yamamoto, Fumihiko Sato, Hidehiko Kumagai, Hiromichi MinamiAbstract:Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield was quite low (
Jun Ishii - One of the best experts on this subject based on the ideXlab platform.
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Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids
Nature Communications, 2019Co-Authors: Christopher J. Vavricka, Takanobu Yoshida, Yuki Kuriya, Teppei Ogawa, Hiromasa Kiyota, Shunsuke Takahashi, Kazuko Agari, Jianyong Li, Jun IshiiAbstract:Previous studies have utilized monoamine oxidase (MAO) and L-3,4-dihydroxyphenylalanine decarboxylase (DDC) for microbe-based production of Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) precursor to opioid analgesics. In the current study, a phylogenetically distinct Bombyx mori 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) is identified to bypass MAO and DDC for direct production of 3,4-dihydroxyphenylacetaldehyde (DHPAA) from L-3,4-dihydroxyphenylalanine (L-DOPA). Structure-based enzyme engineering of DHPAAS results in bifunctional switching between aldehyde synthase and decarboxylase activities. Output of dopamine and DHPAA products is fine-tuned by engineered DHPAAS variants with Phe79Tyr, Tyr80Phe and Asn192His catalytic substitutions. Balance of dopamine and DHPAA products enables improved THP biosynthesis via a symmetrical pathway in Escherichia coli. Rationally engineered insect DHPAAS produces (R,S)-THP in a single enzyme system directly from L-DOPA both in vitro and in vivo, at higher yields than that of the wild-type enzyme. However, DHPAAS-mediated downstream BIA production requires further improvement.
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Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids
Nature communications, 2019Co-Authors: Christopher J. Vavricka, Takanobu Yoshida, Yuki Kuriya, Teppei Ogawa, Hiromasa Kiyota, Shunsuke Takahashi, Kazuko Agari, Fumie Ono, Jun IshiiAbstract:Previous studies have utilized monoamine oxidase (MAO) and L-3,4-dihydroxyphenylalanine decarboxylase (DDC) for microbe-based production of Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) precursor to opioid analgesics. In the current study, a phylogenetically distinct Bombyx mori 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) is identified to bypass MAO and DDC for direct production of 3,4-dihydroxyphenylacetaldehyde (DHPAA) from L-3,4-dihydroxyphenylalanine (L-DOPA). Structure-based enzyme engineering of DHPAAS results in bifunctional switching between aldehyde synthase and decarboxylase activities. Output of dopamine and DHPAA products is fine-tuned by engineered DHPAAS variants with Phe79Tyr, Tyr80Phe and Asn192His catalytic substitutions. Balance of dopamine and DHPAA products enables improved THP biosynthesis via a symmetrical pathway in Escherichia coli. Rationally engineered insect DHPAAS produces (R,S)-THP in a single enzyme system directly from L-DOPA both in vitro and in vivo, at higher yields than that of the wild-type enzyme. However, DHPAAS-mediated downstream BIA production requires further improvement. Bioproduction of Tetrahydropapaveroline (THP) is limited by the specificity of monoamine oxidase (MAO). Here, the authors identify an insect 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) that can bypass MAO for direct aldehyde production and demonstrate bifunctional switching of DHPAAS for efficient THP production.
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Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids
Nature Publishing Group, 2019Co-Authors: Christopher J. Vavricka, Takanobu Yoshida, Yuki Kuriya, Teppei Ogawa, Hiromasa Kiyota, Shunsuke Takahashi, Kazuko Agari, Fumie Ono, Jun IshiiAbstract:Bioproduction of Tetrahydropapaveroline (THP) is limited by the specificity of monoamine oxidase (MAO). Here, the authors identify an insect 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) that can bypass MAO for direct aldehyde production and demonstrate bifunctional switching of DHPAAS for efficient THP production
Michael A. Collins - One of the best experts on this subject based on the ideXlab platform.
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Tetrahydropapaveroline in Parkinson’s Disease and Alcoholism: A Look Back in Honor of Merton Sandler
Neurotoxicology, 2004Co-Authors: Michael A. CollinsAbstract:Although Dr. Merton Sandler's extensive and vigorous research program over the years has been concerned mainly with classical biogenic amines, monoamine oxidase (MAO), and MAO inhibitors, he and his group contributed a significant early Parkinson's disease-related study of a non-classical or "aberrant" biogenic amine. The formation and production of this amine, the dopamine-derived mammalian alkaloid, Tetrahydropapaveroline (THP), is in fact dependent on MAO activity. As reviewed here, that study provided the groundwork for and indeed stimulated many later investigations of mammalian alkaloids in numerous laboratories around the world.
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Tetrahydropapaveroline in parkinson s disease and alcoholism a look back in honor of merton sandler
Neurotoxicology, 2004Co-Authors: Michael A. CollinsAbstract:Although Dr. Merton Sandler's extensive and vigorous research program over the years has been concerned mainly with classical biogenic amines, monoamine oxidase (MAO), and MAO inhibitors, he and his group contributed a significant early Parkinson's disease-related study of a non-classical or "aberrant" biogenic amine. The formation and production of this amine, the dopamine-derived mammalian alkaloid, Tetrahydropapaveroline (THP), is in fact dependent on MAO activity. As reviewed here, that study provided the groundwork for and indeed stimulated many later investigations of mammalian alkaloids in numerous laboratories around the world.
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The in Vitro Formation of 1,3-Dimethyl-1,2,3,4-Tetrahydroisoquinoline, a Neurotoxic Metabolite of Amphetamines
Alzheimer’s and Parkinson’s Diseases, 1995Co-Authors: Hanka Haber, Michael A. Collins, Matthias F. MelzigAbstract:Since the early 1970s interest has been directed towards proposals suggesting the involvement of Pictet-Spengler condensation products, the tetrahydroisoquinolines (TIQ), in the aetiology of alcohol addiction. These products might be formed following alcohol consumption by a condensation between monoamine and an aldehyde, in particular, acetaldehyde. The most studied of all Pictet-Spengler condensation products is salsolinol (1-methyl-6,7-dihydroxy1,2,3,4-tetrahydroisoquinoline), the product of a direct cyclization between dopamine and acetaldehyde. The in vivo formation of Tetrahydropapaveroline by the condensation between dopamine and its deaminated metabolite, 3,4-dihydroxyphenylacetaldehyde (dopaldehyde), has also been postulated (Figure 1).1
