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.
Highlights
Nucleoside analogues, NAs, form a very large family of compounds, with more than 40 presently used in medicine as antiviral and anticancer agents [1,2]
Nucleoside-50 -monophosphates, nucleoside-50 -monophosphates (NMPs), are often used as food additives or intermediates by the pharmaceutical industry. Some dietary nucleotides, such as inosinic acid or guanosinic acid, are common additives used as flavour enhancers in foods, since they induce an umami taste
To classify our recombinant protein, we carried out the enzymatic synthesis of nucleosides using different riboand 20 -deoxyribonucleosides as donors and several purine and pyrimidine bases as acceptors (Table 1)
Summary
Nucleoside analogues, NAs, form a very large family of compounds, with more than 40 presently used in medicine as antiviral and anticancer agents [1,2]. A variety of therapeutic nucleosides and nucleotides, which are in the WHO “List of essential medicines” are produced chemically, such as Abacavir (HIV therapeutic), Capecitabine (anticancer), Cytarabine (anticancer, antiviral), Vidarabine (antiviral), or Floxuridine (anticancer), among others. Nucleoside-50 -monophosphates, NMPs, are often used as food additives or intermediates by the pharmaceutical industry. Some dietary nucleotides, such as inosinic acid (inosine-50 -monophosphate, IMP) or guanosinic acid (guanosine-50 -monophosphate, GMP), are common additives used as flavour enhancers in foods, since they induce an umami taste. 22 of sensation [3]. Current demand for nucleotides in the food additives market is increasing, sensation [3]. Current demand nucleotides in the food additives market is increasing, and the production of nucleotides has beenfor widely studied
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
