Facile Synthesis of Sugar Nucleotides from Common Sugars by the Cascade Conversion Strategy

Abstract

Sugar nucleotides are essential glycosylation donors in the carbohydrate metabolism. Naturally, most sugar nucleotides are derived from a limited number of common sugar nucleotides by de novo biosynthetic pathways, undergoing single or multiple reactions such as dehydration, epimerization, isomerization, oxidation, reduction, amination, and acetylation reactions. However, it is widely believed that such complex bioconversions are not practical for synthetic use due to the high preparation cost and great difficulties in product isolation. Therefore, most of the discovered sugar nucleotides are not readily available. Here, based on de novo biosynthesis mainly, 13 difficult-to-access sugar nucleotides were successfully prepared from two common sugars D-Man and sucrose in high yields, at a multigram scale, and without the need for tedious purification manipulations. This work demonstrated that de novo biosynthesis, although undergoing complex reactions, is also practical and cost-effective for synthetic use by employing a cascade conversion strategy.

Biocatalytic Approaches to Building Blocks for Enzymatic and Chemical Glycan Synthesis

“…Recently, it was reported that such cost-effectiveness (and hence viability for multienzyme cascades) had been further improved through regeneration of the required cofactors (NADH, NADPH, NAD + , PMP, and acetyl-CoA, Figure ). , This has recently been exemplified through the synthesis of 25 challenging to access NDP-sugars starting from mannose, sucrose, and N -acetylglucosamine, in high yield, on a multigram scale, and without the need for purifications. , Additionally, the use of polyphosphate kinase (PPK3) or pyruvate kinase (PK) allows for the regeneration of the nucleotide triphosphates using phosphate glass or phosphoenolpyruvic acid (PEP) as sources of phosphate (Figure ). − Both methods were effective at regenerating ATP used by sugar kinases and UTP/GTP utilized by NDP-sugar pyrophosphorylases.…”

“…Recently, it was reported that such cost-effectiveness (and hence viability for multienzyme cascades) had been further improved through regeneration of the required cofactors (NADH, NADPH, NAD + , PMP, and acetyl-CoA, Figure 2 ). 81 , 82 This has recently been exemplified through the synthesis of 25 challenging to access NDP-sugars starting from mannose, sucrose, and N -acetylglucosamine, in high yield, on a multigram scale, and without the need for purifications. 81 , 82 Additionally, the use of polyphosphate kinase (PPK3) or pyruvate kinase (PK) allows for the regeneration of the nucleotide triphosphates using phosphate glass or phosphoenolpyruvic acid (PEP) as sources of phosphate ( Figure 2 ).…”

Computational Insight into Intraspecies Distinctions in Pseudoalteromonas distincta: Carotenoid-like Synthesis Traits and Genomic Heterogeneity

“…A lot of marine bacterial pigments were investigated for antimicrobial, anti-inflammatory, antioxidant, anti-HSV-1, anticancer, antidiabetic, and wound healing activities, indicating their potential biomedical applications as well as food, feed, cosmetic, and pharmaceutical formulations [ 8 , 9 , 12 ]. In addition, the natural marine pigments and other secondary metabolites could be used as “green chemistry” to replace synthetic compounds [ 11 , 12 , 26 , 27 , 28 , 29 , 30 ].…”

Expanding the Substrate Scope of a Bacterial Nucleotidyltransferase via Allosteric Mutations

“…Wild-type SALTY RmlA accepts diverse α- d -hexose-1-phosphates, including all monodeoxy α- d -Glc-1-phosphates, to produce various dTDP-sugars . Elegant work by Thorson and co-workers demonstrated that rational and evolved mutations in SALTY RmlA could provide access to an even broader pool of NDP-sugars, including ADP- and GDP-sugars and dTDP-unnatural sugars. − Others have expanded this nucleotide sugar pool through the use of RmlA homologues that also demonstrate a lack of substrate specificity. ,− While diverse nucleotide sugars have been produced through chemoenzymatic routes, there have been limitations in the efficiency of a single enzyme to produce different NDP-sugars, especially with noncanonical substrates. , …”

“…32−36 Others have expanded this nucleotide sugar pool through the use of RmlA homologues that also demonstrate a lack of substrate specificity. 2,37−39 While diverse nucleotide sugars have been produced through chemoenzymatic routes, 40 there have been limitations in the efficiency of a single enzyme to produce different NDP-sugars, especially with noncanonical substrates. 25,26 One key limitation to the catalytic efficiency of RmlA is product inhibition by dTDP-α-Glc or negative feedback regulation by dTDP-β-L-Rha via allosteric site binding (Figure 1B).…”