“…Modified nucleosides have been traditionally synthesized by different chemical methods, requiring the use of protection-deprotection steps, organic solvents and chemical reagents [4][5][6][7][8][9][10][11]. In this sense, LdNDT has shown to be an interesting sustainable alternative to traditional chemical methods for the synthesis of many different purine nucleosides.…”
Section: Discussionmentioning
confidence: 99%
“…NAs and NMPs have been traditionally synthesized by chemical methods through multistep processes requiring protection and de-protection steps for the labile groups, and isolation in almost every step due to the poor regio-or stereoselectivity of the reactions [4][5][6][7][8]. These drawbacks lead to a high price of these valuable compounds, limiting their application.…”
Section: Introductionmentioning
confidence: 99%
“…In this context, the enzymatic synthesis of NAs and NMPs shows many advantages, such as one-pot reactions under mild conditions, high stereo-, and regioselectivity, and an environmentally friendly technology [4][5][6][7][8][9][10][11].…”
Abstract:Biocatalysis reproduce nature's synthetic strategies in order to synthesize different organic compounds. Natural metabolic pathways usually involve complex networks to support cellular growth and survival. In this regard, multi-enzymatic systems are valuable tools for the production of a wide variety of organic compounds. Methods: The production of different purine nucleosides and nucleoside-5 -monophosphates has been performed for first time, catalyzed by the sequential action of 2 -deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) and hypoxanthine-guanine-xanthine phosphoribosyltransferase from Thermus themophilus HB8 (TtHGXPRT). Results: The biochemical characterization of LdNDT reveals that the enzyme is active and stable in a broad range of pH, temperature, and ionic strength. Substrate specificity studies showed a high promiscuity in the recognition of purine analogues. Finally, the enzymatic production of different purine derivatives was performed to evaluate the efficiency of multi-enzymatic system LdNDT/TtHGXPRT. Conclusions: The production of different therapeutic purine nucleosides was efficiently catalyzed by LdNDT/TtHGXPRT. In addition, the resulting by-products were converted to IMP and GMP. Taking all of these features, this bioprocess entails an efficient, sustainable, and economical alternative to chemical synthetic methods.
“…Modified nucleosides have been traditionally synthesized by different chemical methods, requiring the use of protection-deprotection steps, organic solvents and chemical reagents [4][5][6][7][8][9][10][11]. In this sense, LdNDT has shown to be an interesting sustainable alternative to traditional chemical methods for the synthesis of many different purine nucleosides.…”
Section: Discussionmentioning
confidence: 99%
“…NAs and NMPs have been traditionally synthesized by chemical methods through multistep processes requiring protection and de-protection steps for the labile groups, and isolation in almost every step due to the poor regio-or stereoselectivity of the reactions [4][5][6][7][8]. These drawbacks lead to a high price of these valuable compounds, limiting their application.…”
Section: Introductionmentioning
confidence: 99%
“…In this context, the enzymatic synthesis of NAs and NMPs shows many advantages, such as one-pot reactions under mild conditions, high stereo-, and regioselectivity, and an environmentally friendly technology [4][5][6][7][8][9][10][11].…”
Abstract:Biocatalysis reproduce nature's synthetic strategies in order to synthesize different organic compounds. Natural metabolic pathways usually involve complex networks to support cellular growth and survival. In this regard, multi-enzymatic systems are valuable tools for the production of a wide variety of organic compounds. Methods: The production of different purine nucleosides and nucleoside-5 -monophosphates has been performed for first time, catalyzed by the sequential action of 2 -deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) and hypoxanthine-guanine-xanthine phosphoribosyltransferase from Thermus themophilus HB8 (TtHGXPRT). Results: The biochemical characterization of LdNDT reveals that the enzyme is active and stable in a broad range of pH, temperature, and ionic strength. Substrate specificity studies showed a high promiscuity in the recognition of purine analogues. Finally, the enzymatic production of different purine derivatives was performed to evaluate the efficiency of multi-enzymatic system LdNDT/TtHGXPRT. Conclusions: The production of different therapeutic purine nucleosides was efficiently catalyzed by LdNDT/TtHGXPRT. In addition, the resulting by-products were converted to IMP and GMP. Taking all of these features, this bioprocess entails an efficient, sustainable, and economical alternative to chemical synthetic methods.
“…The optimization of immobilization and reaction parameters allowed reaching a productivity of 138 mg L −1 hr −1 . NDTs, in comparison with nucleoside NPs, have the ability of catalyzing transglycosylation reactions between purine or pyrimidine bases and nucleosides in one step instead of two, and one‐pot one‐step transglycosylations are more advantageous than those based on nucleoside phosphorylases . Interestingly, NDT activity by this bacterial genre is first described in this work, the activity found suggests it is a NDT Type II.…”
Section: Resultsmentioning
confidence: 66%
“…These analogues were originally synthesized by chemical methods that required the use of organic solvents, many reaction steps and the removal of protecting groups . In this sense, biocatalysis emerged as an alternative to these problems due to their high catalytic efficiency and selectivity, taking place under very mild conditions and offering an environmentally clean technology …”
Cladribine is a nucleoside analogue widely used in the pharmaceutical industry for the treatment of several neoplasms, including hairy‐cell leukemia among others. This compound has also shown efficacy in the treatment of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. In this work, a green bioprocess for cladribine biosynthesis using immobilized Arthrobacter oxydans was developed. The microorganism was stabilized by entrapment immobilization in the natural matrix alginate. Different reaction parameters were optimized obtaining a biocatalyst able to achieve cladribine bioconversion values close to 85% after 1 hr, the shortest reaction times reported so far. The developed bioprocess was successfully scaled‐up reaching a productivity of 138 mg L−1 hr−1. Also, the biocatalyst was stable for 5 months in storage and in 96 hr at operational conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.