Enzymatic synthesis of vancomycin derivatives using galactosyltransferase and sialyltransferase

Oh, Tae‐Jin; Kim, Dae–Hee; Kang, Sun Youp; Yamaguchi, Tokutaro; Sohng, Jae Kyung

doi:10.1038/ja.2010.131

Cited by 21 publications

(15 citation statements)

References 25 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because of both our ongoing studies with PUFAs and the many reported bioactivities of DHA and EDPs, we sought an operationally simple and cost-effective method to access both enantiomers of two EDP regioisomers, 16,17-and 19,20-EDP, without recourse to total synthesis or chiral separations. Enzymatic synthesis has become a popular method to access both single enantiomers of molecules and compounds that are otherwise difficult to prepare by conventional synthetic means and have been used successfully in esterifications (40), glycosylations (41), aldol reactions (42), and kinetic resolutions (43) and have even been used on an industrial scale (44). Enzymes are operationally simple to use, have fast reaction times, use mild conditions, and are environmentally benign (aqueous reactions; lack of heavy metal catalysts or toxic solvents).…”

Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Cinelli

Yang

Scharmen

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

Epoxy PUFAs are endogenous cytochrome P450 (P450) metabolites of dietary PUFAs. Although these metabolites exert numerous biological effects, attempts to study their complex biology have been hampered by difficulty in obtaining the epoxides as pure regioisomers and enantiomers. To remedy this, we synthesized 19,20- and 16,17-epoxydocosapentaenoic acids (EDPs) (the two most abundant EDPs in vivo) by epoxidation of DHA with WT and the mutant (F87V) P450 enzyme BM3 from WT epoxidation yielded a 4:1 mixture of 19,20:16,17-EDP exclusively as (,) enantiomers. Epoxidation with the mutant (F87V) yielded a 1.6:1 mixture of 19,20:16,17-EDP; the 19,20-EDP fraction was ∼9:1 (,):(,), but the 16,17-EDP was exclusively the (,) enantiomer. To access the (,) enantiomers of these EDPs, we used a short (four-step) chemical inversion sequence, which utilizes 2-(phenylthio)ethanol as the epoxide-opening nucleophile, followed by mesylation of the resulting alcohol, oxidation of the thioether moiety, and base-catalyzed elimination. This short synthesis cleanly converts the (,)-epoxide to the (,)-epoxide without loss of enantiopurity. This method, also applicable to eicosapentaenoic acid and arachidonic acid, provides a simple, cost-effective procedure for accessing larger amounts of these metabolites.

show abstract

Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Cinelli

Yang

Scharmen

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…297 The rapid global emergence of vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA) has inspired the development of novel glycopeptides with improved activity against resistant strains, 298-300 highlighting the influence of vancomycin's (177) a-Lvancosaminyl-(1,2)-b-D-glucosyl disaccharide modification in circumventing key resistance mechanisms. 238,251,[301][302][303][304] Whether this established precedent for improving glycopeptide therapeutics via glycosylation will hold true for related antibiotics, such as the lipopeptide daptomycin, 305 remains to be determined.…”

Section: Libraries Based Upon Inherent Biosynthetic Glycosyltransferasesmentioning

confidence: 99%

Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules

2011

View full text Add to dashboard Cite

Glyco (randomization/diversification) is a term that encompasses strategies to diversify a core drug scaffold via enzymatic glycosylation to provide sets of analogs wherein the sole diversity element is a carbohydrate. This review covers the influence of glycosylation upon various drug properties, the classes of glycosyl-conjugating enzymes amenable to glyco(randomization/diversification) schemes, approaches to the synthesis of required substrates and specific examples of glycorandomized libraries utilizing both wild-type and engineered enzymes.

show abstract

“…6 The selection for this model was based upon the known impact of sugar modification upon improving the activity of vancomycin analogs against vancomycin-resistance bacteria, 4f,7 and the permissive nature of the vancomycin GT GtfE. 8 Vancomycin aglycon ( 3 ) was readily obtained by acid hydrolysis of vancomycin.…”

mentioning

confidence: 99%

Natural Product Disaccharide Engineering through Tandem Glycosyltransferase Catalysis Reversibility and Neoglycosylation

et al. 2012

View full text Add to dashboard Cite

A two-step strategy for disaccharide modulation using vancomycin as a model is reported. The strategy relies upon a glycosyltransferase-catalyzed ‘reverse’ reaction to enable the facile attachment of an alkoxyamine-bearing sugar to the vancomycin core. Neoglycosylation of the corresponding aglycon led to a novel set of vancomycin 1,6-disaccharide variants. While the in vitro antibacterial properties of corresponding vancomycin 1,6-disaccharide analogs were equipotent to the parent antibiotic, the chemoenzymatic method presented is expected to be broadly applicable.

show abstract

Enzymatic synthesis of vancomycin derivatives using galactosyltransferase and sialyltransferase

Cited by 21 publications

References 25 publications

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules

Natural Product Disaccharide Engineering through Tandem Glycosyltransferase Catalysis Reversibility and Neoglycosylation

Contact Info

Product

Resources

About