Development of a nanostabilized biocatalyst using an extremophilic microorganism for ribavirin biosynthesis

Benedetti, Eliana C. De; Rivero, Cintia W.; Trelles, Jorge A.

doi:10.1016/j.molcatb.2015.08.006

Cited by 12 publications

(7 citation statements)

References 33 publications

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“…The synthesis of Ribavirin (1) by enzymatic transglycosylation was performed both by using whole cells (e.g., Escherichia coli, A. hydrophila, Enterobacter aerogenes, Enterobacter gergoviae) and isolated PNPs [22][23][24][25][26][27][28][29][30][31][32][33]. Either natural nucleosides or the suitable sugar phosphates were used as the ribose donor, resulting in variable yields (from 19% to 84%).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation

et al. 2019

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Despite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a “one-pot, one-enzyme” transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2′-deoxy counterpart were synthesized and incubated either with the “purine-like” base or the modified purine of the three selected APIs. Good conversions (49–67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepared with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were observed. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-N6-cyclopentyladenosine, or CCPA. Only the formation of CCPA was observed (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of AhPNP.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation

et al. 2019

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“…As is well known, some bionanocomposites such as bentonite have shown improvements in the biocatalyst stability and its mechanical properties when they are incorporated into a matrix such as agarose or a hydrogel such as alginate (Cappa and Trelles 2017;De Benedetti et al 2015), usually without signi cantly affecting the biocatalyst activity. Stability improvements of the biocatalyst were evidenced in reusability and storage assays, in which the biocatalysts entrapped in matrices that included bentonite showed the best behavior.…”

Section: Discussionmentioning

confidence: 99%

Decitabine bioproduction using a biocatalyst with improved stability by adding nanocomposites

Méndez

Trelles

Rivero

2020

Preprint

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A novel IDA-LaNDT derivative was able to reach the highest productivity in the biosynthesis of a well-known antitumoral agent called decitabine. However, the combination of two simple and inexpensive techniques such as ionic absorption and gel entrapment with the incorporation of a bionanocomposite such as bentonite significantly improved the stability of this biocatalyst. These modifications allowed the enhancement of storage stability (for at least 18 months), reusability (400 h of successive batches without significant loss of its initial activity), and thermal and solvent stability with respect to the non-entrapped derivative. Moreover, reaction conditions were optimized by increasing the solubility of 5-aza by dilution with dimethylsulfoxide. Therefore, a scale-up of the bioprocess was assayed using the developed biocatalyst, obtaining 221 mg/L.h of DAC. Finally, green parameters were calculated using the nanostabilized biocatalyst, whose results indicated that it was able to biosynthesize DAC by a smooth, cheap, and environmentally friendly methodology.

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“…However, when the derivative achieved its maximum conversion, after 5 h of reaction, the immobilized biocatalysts reached similar productivities. It is well known that this difference in reaction rate, mainly at the beginning of the reaction, is related to diffusion restrictions of this kind of matrix (Rivero et al 2012 ; De Benedetti et al 2015 ). However, this slight decrease in the reaction rate is offset by the increase in the number of reuses, in storage stability and in thermal and solvent stability, which was accomplished by the immobilization process.…”

Section: Discussionmentioning

confidence: 99%

Decitabine bioproduction using a biocatalyst with improved stability by adding nanocomposites

2020

Self Cite

View full text Add to dashboard Cite

A novel IDA-LaNDT derivative was able to reach the highest productivity in the biosynthesis of a well-known antitumoral agent called decitabine. However, the combination of two simple and inexpensive techniques such as ionic absorption and gel entrapment with the incorporation of a bionanocomposite such as bentonite significantly improved the stability of this biocatalyst. These modifications allowed the enhancement of storage stability (for at least 18 months), reusability (400 h of successive batches without significant loss of its initial activity), and thermal and solvent stability with respect to the non-entrapped derivative. Moreover, reaction conditions were optimized by increasing the solubility of 5-aza by dilution with dimethylsulfoxide. Therefore, a scale-up of the bioprocess was assayed using the developed biocatalyst, obtaining 221 mg/L·h of DAC. Finally, green parameters were calculated using the nanostabilized biocatalyst, whose results indicated that it was able to biosynthesize DAC by a smooth, cheap, and environmentally friendly methodology.

show abstract

Development of a nanostabilized biocatalyst using an extremophilic microorganism for ribavirin biosynthesis

Cited by 12 publications

References 33 publications

Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation

Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation

Decitabine bioproduction using a biocatalyst with improved stability by adding nanocomposites

Decitabine bioproduction using a biocatalyst with improved stability by adding nanocomposites

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