Glycosyltransferase cascades for natural product glycosylation: Use of plant instead of bacterial sucrose synthases improves the UDP‐glucose recycling from sucrose and UDP

Gutmann, Alexander; Lepak, Alexander J.; Diricks, Margo; Desmet, Tom; Nidetzky, Bernd

doi:10.1002/biot.201600557

Cited by 41 publications

(33 citation statements)

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“…The expensive UDP‐sugar donor is a critical problem limiting the in vitro glycosylation of natural products. To solve this problem, a sucrose synthase can be coupled with a glycosylation reaction, which allows the consumption of inexpensive sucrose to provide UDP‐Glc by recycling UDP (Gutmann, Lepak, Diricks, Desmet, & Nidetzky, 2017; Gutmann & Nidetzky, 2016; Schmolzer, Gutmann, Diricks, Desmet, & Nidetzky, 2016; Schmolzer, Lemmerer, & Nidetzky, 2018). Notably, this system can provide a similar glycosylation reaction environment in cells, which provides a powerful tool for investigating the real catalytic performance of UGT.…”

Section: Resultsmentioning

confidence: 99%

Mining of UDP‐glucosyltrfansferases in licorice for controllable glycosylation of pentacyclic triterpenoids

Zhang

Ren

Liu

et al. 2020

Biotech & Bioengineering

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Pentacyclic triterpenoids have wide applications in the pharmaceutical industry. The precise glucosylation at C-3 OH of pentacyclic triterpenoids mediated by uridine 5'-diphospho-glucosyltransferase (UDP-glucosyltransferase [UGT]) is an important way to produce valuable derivatives with various improved functions. However, most reported UGTs suffer from low regiospecificity toward the OH and COOH groups of pentacyclic triterpenoids, which significantly decreases the

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Section: Resultsmentioning

confidence: 99%

Mining of UDP‐glucosyltrfansferases in licorice for controllable glycosylation of pentacyclic triterpenoids

Zhang

Ren

Liu

et al. 2020

Biotech & Bioengineering

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“…The binding of the sugar or aglycone acceptor results in an enzyme-substrate ternary complex [41]. Hydrolysis of the sugar nucleotide donor is prevented by the tight binding in an unproductive state, where the high affinity of the enzyme for the sugar nucleotide donor is an indicator for product inhibition (K i ) by the released nucleotide [42]. For Leloir glycosyltransferases, a lower affinity or promiscuity towards the nucleotide donor results often in less product inhibition [43].…”

Section: Glycosyltransferases In Naturementioning

confidence: 99%

“…The thermodynamic constraints of enzymatic glycosylations of sugar acceptors with nucleotide donors for the synthesis of di-, oligo-, or polysaccharides has been explored to a lesser extent. Sucrose synthase has been employed for the regeneration of nucleotide sugars [25,42,80,176,177]. The equilibrium constant (K eq ) of the reaction of sucrose with UDP to afford the sugar donor UDP-glucose was determined [178].…”

Section: Application Of Glycosyl Transferases In Organic Synthesismentioning

confidence: 99%

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Mestrom

Przypis

Kowalczykiewicz

et al. 2019

IJMS

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Enzymes are nature's catalyst of choice for the highly selective and efficient coupling of carbohydrates. Enzymatic sugar coupling is a competitive technology for industrial glycosylation reactions, since chemical synthetic routes require extensive use of laborious protection group manipulations and often lack regio-and stereoselectivity. The application of Leloir glycosyltransferases has received considerable attention in recent years and offers excellent control over the reactivity and selectivity of glycosylation reactions with unprotected carbohydrates, paving the way for previously inaccessible synthetic routes. The development of nucleotide recycling cascades has allowed for the efficient production and reuse of nucleotide sugar donors in robust one-pot multi-enzyme glycosylation cascades. In this way, large glycans and glycoconjugates with complex stereochemistry can be constructed. With recent advances, LeLoir glycosyltransferases are close to being applied industrially in multi-enzyme, programmable cascade glycosylations.hydroxynitrile lyases catalyzed the enzymatic hydrolysis of the glycoside amygdalin [3]. Moving almost two centuries forward, the largest volumetric biocatalytic industrial process is the application of glucose isomerase for the production of high fructose syrup for food and drink applications, producing fructose from glucose at 10 7 tons per year [4]. The secret of the success of enzymes in the production or treatment of carbohydrates and glycosides is their exquisite stereo-and regioselectivity. The excellent selectivity of enzymes is required due to the diversity of structural features of carbohydrates [5], comprising d-and l-epimers, ring size, anomeric configuration, linkages, branching, and oxidation state(s). Since drug targets often exhibit specificity for all of these structural features, the production process should not contain any side-products to prevent undesired side-effects [6].The challenge in the synthesis of carbohydrates is their wide variety of functionalities and stereochemistry ( Figure 1). (Poly)hydroxyaldehydes containing a terminal aldehyde are referred to as aldoses and (poly)hydroxyketones are defined as ketoses. In aqueous solutions, monosaccharides form equilibrium mixtures of linear open-chain and ring-closed 5-or 6-membered furanoses or pyranoses, respectively. For aldoses, the asymmetric ring forms at C-1. For ketoses, it closes at C-2 as an axial (α) or equatorial (β) hemiacetal or hemiketal, respectively (commonly defined as the anomeric center). A glycosidic linkage is a covalent O-, S-, N-, or C-bond connecting a monosaccharide to another residue resulting in a glycoside, while glucoside is specific for a glucose moiety. The equatorial or axial position of the glycosidic bond is referred to as α-(axial) or β-linkage (equatorial). The number of carbohydrates linked via glycosidic bonds can be subdivided into oligosaccharides with two to ten linked carbohydrates, while polysaccharides (glycans) contain more than ten glycosidic bonds. A glycan either con...

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“…In all organisms, however, UGTs selectively catalyse the transfer of a sugar from activated nucleotide-sugar donor molecules (usually UDP glucose in plants) to an acceptor molecule without the need for protective groups. Biocatalytic processes involving UGTs thus represent an interesting alternative to chemical synthesis of glycosides 24,25,35,36 .…”

Section: Introductionmentioning

confidence: 99%

Novel biotechnological glucosylation of high-impact aroma chemicals, 3(2H)- and 2(5H)-furanones

Effenberger

Hoffmann

Jonczyk

et al. 2019

Sci Rep

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Glucosyltransferases are versatile biocatalysts to chemically modify small molecules and thus enhance their water solubility and structural stability. Although the genomes of all organisms harbor a multitude of glucosyltransferase genes, their functional characterization is hampered by the lack of high-throughput in-vivo systems to rapidly test the versatility of the encoded proteins. We have developed and applied a high-throughput whole cell biotransformation system to screen a plant glucosyltransferase library. As proof of principle, we identified 25, 24, 15, and 18 biocatalysts transferring D-glucose to sotolone, maple furanone, furaneol and homofuraneol, four highly appreciated flavor compounds, respectively. Although these 3(2H)- and 2(5H)-furanones have extremely low odor thresholds their glucosides were odorless. Upscaling of the biotechnological process yielded titers of 5.3 and 7.2 g/L for the new to nature β-D-glucopyranosides of sotolone and maple furanone, respectively. Consequently, plant glucosyltransferase show stunning catalytic activities, which enable the economical production of novel and unexplored chemicals with exciting new functionalities by whole-cell biotransformation.

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Glycosyltransferase cascades for natural product glycosylation: Use of plant instead of bacterial sucrose synthases improves the UDP‐glucose recycling from sucrose and UDP

Cited by 41 publications

References 50 publications

Mining of UDP‐glucosyltrfansferases in licorice for controllable glycosylation of pentacyclic triterpenoids

Mining of UDP‐glucosyltrfansferases in licorice for controllable glycosylation of pentacyclic triterpenoids

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Novel biotechnological glucosylation of high-impact aroma chemicals, 3(2H)- and 2(5H)-furanones

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