Nucleotide-based Production Service
Nucleotides are compounds made up of purine/pyrimidine bases, deoxyribose/ribose, and phosphoric acid. There is one phosphate group that exists in nucleoside monophosphate (NMP). The 5'-nucleotide phosphate group can be further phosphorylated to generate nucleoside diphosphate (NDP) and nucleoside triphosphate (NTP), and the phosphate groups are linked by high-energy bonds.
Nucleotides are the precursors of biological macromolecules DNA, RNA, and participate in the heredity, developmental, and growth activities of organisms as the constituent parts of nucleic acids. In addition, many nucleotides are involved in various important biological functions, such as adenosine triphosphate (ATP), coenzymes, and others related to energy metabolism. Some nucleotide derivatives can interfere with nucleotide metabolism and have broad application prospects as anticancer drugs.
Fig.1 Chemical structures of NMP, NDP, and NTP. (CD BioGlyco)
We deploy integrated chemical and enzymatic methodologies to advance nucleotide synthesis. Our platform synthesizes nucleotides through solution-phase and solid-supported techniques. A pivotal innovation involves single-step condensation reactions that circumvent conventional multi-step synthetic routes. This approach utilizes specialized reagents to construct sugar-nucleotides from commercial precursors with exceptional regioselectivity.
Biocatalytic transformations further expand our capabilities. While typically restricted to natural substrates, our enzymatic processes enable gram-scale nucleotide production. We integrate high-concentration multi-enzyme cascades with selective precipitation purification, a chromatography-free strategy optimized for industrial-scale throughput. This synergistic fusion of chemical precision and enzymatic efficiency empowers us to tackle diverse nucleoside analogs and synthetically challenging targets.
In the spirit of quality first, service first, CD BioGlyco is committed to producing various high-purity nucleotides for customers. We have NMP, NDP, and NTP production services, as well as nucleotide derivative production services according to your specific needs.
There is one phosphate group in the NMP molecule. Guanosine monophosphate (GMP) has a taste property, with the ability to be a condiment. Milk powder is rich in NMP, which plays a role in improving the immunomodulatory capacity and memory of infants. We deliver end-to-end synthesis of NMPs, combining enzymatic precision with scalable processes:
NDP is obtained by adding a high-energy bonded phosphate group to NMP. ADP is a component of Coenzyme I/II. UDP is mainly used as an activated intermediate, such as UDP-glucose and CDP-ethanolamine.
NTP with three phosphate groups in the molecule is the universal energy currency. ATP is the most common; UTP functions in glycogen synthesis, CTP provides energy in phospholipid synthesis, and GTP plays a role in protein synthesis.
Nucleotide derivatives are of great value in various fields. Their powerful therapeutic effects have been shown in diseases such as cancer, cardiovascular disease, inflammation, and viral infection. In addition, they also have extensive and stable nutritional and health care functions.
Prepare nucleoside and sugar substrates by dissolving them in appropriate buffers (e.g., phosphate buffer) at optimal concentrations, ensuring purity through filtration or chromatography if necessary.
Select specific glycosyltransferases or nucleotidyltransferases (depending on the target nucleoside-sugar) and activate them by reconstituting in a buffer with cofactors to initiate catalytic activity.
Combine the prepared nucleoside, sugar, activated enzyme, and cofactors in a reaction vessel, adjusting pH and temperature to match the enzyme's optimal conditions.
Incubate the mixture under controlled conditions to allow the enzymatic reaction, where the sugar moiety is transferred to the nucleoside. Monitor progress periodically using analytical techniques to track product formation.
Stop the reaction once the desired yield is achieved by methods such as heat inactivation, adding denaturing agents, or adjusting pH to extremes.
Separate the nucleoside-sugar product from unreacted substrates, enzymes, and by-products using purification steps like column chromatography, solvent extraction, or precipitation.
Confirm the identity and purity of the purified nucleoside-sugar using spectroscopic methods and quantify the yield via HPLC with a standard curve or UV-visible spectroscopy.
DOI.: 10.1021/acssynbio.3c00737
Journal: ACS Synthetic Biology
IF: 3.9
Published: 2024
Results: This review details advances in engineering nucleotide sugar metabolism in Saccharomyces cerevisiae to enable glycosylation of natural products. The authors propound methodologies broadening yeast's endogenous UDP-sugar repertoire, constrained strictly to UDP-glucose and UDP-galactose, through salvage avenues (exploiting exogenous sugars) and de novo routes (wherein existing nucleotides undergo enzymatic interconversions). Key challenges include overcoming feedback inhibition mechanisms (e.g., UDP-xylose suppressing UDP-glucuronic acid synthesis) and engineering promiscuous glycosyltransferases. Successful applications include producing glycosylated terpenoids (e.g., saponins, steviol glycosides) and flavonoids (e.g., scutellarin) by expressing heterologous enzymes. The work highlights yeast's potential as a chassis for synthesizing bioactive glycosides with therapeutic value.
Our nucleotide production delivers high-purity nucleotides tailored for therapeutic and diagnostic research. To extend their functional utility, we offer Phosphate Group-based Modification Services that engineer stability, reactivity, and targeting properties:
CD BioGlyco provides Custom Carbohydrate Synthesis services and exclusive solutions for clients. If you are interested in our nucleotide-based production service or Glyco™ Synthesis Platform, please feel free to contact us for more information.
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