Synthesis and Characterization of Metabolites and Potential Impurities of Balsalazide Disodium, an Anti-Inflammatory Drug

Khan, Md Umar; Baseer, Mohammad Abdul; Kumar, Sanjai; Marimuthu, Saravanakumar; Prasannanjali, A. G.; Gupta, P. Badarinadh; Kaushik, Vipin K.; Handa, V. K.; Islam, Aminul

doi:10.1080/00397910903221068

Cited by 15 publications

(5 citation statements)

References 12 publications

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“…Beta-alanine is a desired precursor for the synthesis of different polymers in the chemical industry (i.e., polyacrylamide, polyacrylate, polyacrylonitrile, and nylon-3) ( Könst et al, 2009 ; Steunenberg et al, 2013 ; Ko et al, 2020 ). In addition, beta-alanine has commercial relevance as a nutritional supplement and is a precursor of pantothenate (vitamin B 5 ), coenzyme A and pharmaceutical drugs ( Khan et al, 2010 ; Trexler et al, 2015 ). In prokaryotes, beta-alanine is mainly produced by decarboxylation of L-aspartate by L-aspartate 1-decarboxylase ( Cronan, 1980 ) ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Production of biopolymer precursors beta-alanine and L-lactic acid from CO2 with metabolically versatile Rhodococcus opacus DSM 43205

Salusjärvi

Ojala²,

Peddinti³

et al. 2022

Front. Bioeng. Biotechnol.

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Hydrogen oxidizing autotrophic bacteria are promising hosts for conversion of CO2 into chemicals. In this work, we engineered the metabolically versatile lithoautotrophic bacterium R. opacus strain DSM 43205 for synthesis of polymer precursors. Aspartate decarboxylase (panD) or lactate dehydrogenase (ldh) were expressed for beta-alanine or L-lactic acid production, respectively. The heterotrophic cultivations on glucose produced 25 mg L−1 beta-alanine and 742 mg L−1 L-lactic acid, while autotrophic cultivations with CO2, H2, and O2 resulted in the production of 1.8 mg L−1 beta-alanine and 146 mg L−1 L-lactic acid. Beta-alanine was also produced at 345 μg L−1 from CO2 in electrobioreactors, where H2 and O2 were provided by water electrolysis. This work demonstrates that R. opacus DSM 43205 can be engineered to produce chemicals from CO2 and provides a base for its further metabolic engineering.

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Section: Introductionmentioning

confidence: 99%

Production of biopolymer precursors beta-alanine and L-lactic acid from CO2 with metabolically versatile Rhodococcus opacus DSM 43205

Salusjärvi

Ojala²,

Peddinti³

et al. 2022

Front. Bioeng. Biotechnol.

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“…2,3 Furthermore, β-alanine is also used as a satisfying supplement for humans to form a histidinecontaining dipeptide, such as carnosine, which is present in the muscle and the brain tissue of humans. 4,5 At present, βalanine is widely applied in the synthesis of pharmaceuticals such as pamidronic acid, 6 guanidinopropionic acid and balsalazide, 7 and feed and food additives.…”

Section: ■ Introductionmentioning

confidence: 99%

“…β-Alanine, as an important component of pantothenic acids, is a key intermediate for the synthesis of coenzyme A and the acyl-carrier protein, which play roles in carrying acetyl and acyl groups and their transfer, respectively . The mutants deficient in the biosynthesis of β-alanine are lethal because they are unable to synthesis coenzyme A. , Furthermore, β-alanine is also used as a satisfying supplement for humans to form a histidine-containing dipeptide, such as carnosine, which is present in the muscle and the brain tissue of humans. , At present, β-alanine is widely applied in the synthesis of pharmaceuticals such as pamidronic acid, guanidinopropionic acid and balsalazide, and feed and food additives.…”

Section: Introductionmentioning

confidence: 99%

Rerouting Fluxes of the Central Carbon Metabolism and Relieving Mechanism-Based Inactivation of l-Aspartate-α-decarboxylase for Fermentative Production of β-Alanine in Escherichia coli

Zhang

Wang

et al. 2022

ACS Synth. Biol.

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β-Alanine, with the amino group at the β-position, is an important platform chemical that has been widely applied in pharmaceuticals and feed and food additives. However, the current modest titer and productivity, increased fermentation cost, and complicated operation are the challenges for producing β-alanine by microbial fermentation. In this study, a high-yield β-alanineproducing strain was constructed by combining metabolic engineering, protein engineering, and fed-batch bioprocess optimization strategies. First, an aspartate-α-decarboxylase from Bacillus subtilis was introduced in Escherichia coli W3110 to construct an initial β-alanine-producing strain. Production of βalanine was obviously increased to 4.36 g/L via improving the metabolic flux and reducing carbon loss by rerouting fluxes of the central carbon metabolism. To further increase β-alanine production, mechanism-based inactivation of aspartate-α-decarboxylase was relieved by rational design to maintain the productivity at a high level in β-alanine fed-batch fermentation. Finally, fed-batch bioprocess optimization strategies were used to improve β-alanine production to 85.18 g/L with 0.24 g/g glucose yield and 1.05 g/ L/h productivity in fed-batch fermentation. These strategies can be effectively used in the construction of engineered strains for βalanine and production of its derivatives, and the final engineered strain was a valuable microbial cell factory that can be used for the industrial production of β-alanine.

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“…polyacrylamide, polyacrylate, polyacrylonitrile and nylon-3) [32][33][34]. In addition, beta-alanine has commercial relevance as a nutritional supplement and is a precursor of pantothenate (vitamin B 5 ), coenzyme A and pharmaceutical drugs [35,36]. L-lactic acid selected as a second production target is used as a precursor for the production of polymers and has multiple applications in chemical and other industries [37].…”

Section: Introductionmentioning

confidence: 99%

Production of Biopolymer Precursors Beta-Alanine And L-Lactic Acid From CO2 With Metabolically Versatile Rhodococcus Opacus DSM 43205

Salusjärvi

Ojala

Peddinti

et al. 2022

Preprint

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Background: Hydrogen-oxidizing autotrophic bacteria are promising hosts for conversion of CO2 into chemicals. In this work, we engineered the metabolically versatile lithoautotrophic bacterium Rhodococcus opacus strain DSM 43205 for synthesis of polymer precursors. Either, a gene encoding aspartate decarboxylase (panD) or lactate dehydrogenase (ldh) were expressed for autotrophic and heterotrophic beta-alanine or L-lactic acid production, respectively.Results: Heterotrophic cultivations on glucose yielded 25 mg L-1 beta-alanine and 742 mg L-1 L-lactic acid, while under autotrophic cultivation conditions with the gaseous substrates CO2, H2 and O2, beta-alanine and L-lactic acid concentrations were 1.8 mg L-1 and 146 mg L-1, respectively. In electrobioreactors, where H2 and O2 were produced in situ by water electrolysis, a beta-alanine titer of 345 µg L-1 was reached from CO2.Conclusions: We demonstrate successful production of beta-alanine and L-lactic acid from CO2. This work demonstrates that R. opacus DSM 43205 can be readily engineered for the autotrophic production of chemicals and provides a basis for further metabolic engineering of its autotrophic metabolism to increase productivity and yield.

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Synthesis and Characterization of Metabolites and Potential Impurities of Balsalazide Disodium, an Anti-Inflammatory Drug

Cited by 15 publications

References 12 publications

Production of biopolymer precursors beta-alanine and L-lactic acid from CO2 with metabolically versatile Rhodococcus opacus DSM 43205

Production of biopolymer precursors beta-alanine and L-lactic acid from CO2 with metabolically versatile Rhodococcus opacus DSM 43205

Rerouting Fluxes of the Central Carbon Metabolism and Relieving Mechanism-Based Inactivation of l-Aspartate-α-decarboxylase for Fermentative Production of β-Alanine in Escherichia coli

Production of Biopolymer Precursors Beta-Alanine And L-Lactic Acid From CO2 With Metabolically Versatile Rhodococcus Opacus DSM 43205

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