NDP-rhamnose biosynthesis and rhamnosyltransferases: building diverse glycoconjugates in nature

TY - JOUR

T1 - NDP-rhamnose biosynthesis and rhamnosyltransferases

T2 - building diverse glycoconjugates in nature

AU - Wagstaff, Ben A.

AU - Zorzoli, Azul

AU - Dorfmueller, Helge C.

N1 - Funding Information: This research was funded in whole by the Wellcome Trust [Grant number 109357/Z/15/Z and 105606/Z/14/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: © 2021 The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - Rhamnose is an important 6-deoxy sugar present in many natural products, glycoproteins, and structural polysaccharides. Whilst predominantly found as the l-enantiomer, instances of d-rhamnose are also found in nature, particularly in the Pseudomonads bacteria. Interestingly, rhamnose is notably absent from humans and other animals, which poses unique opportunities for drug discovery targeted towards rhamnose utilizing enzymes from pathogenic bacteria. Whilst the biosynthesis of nucleotide-activated rhamnose (NDP-rhamnose) is well studied, the study of rhamnosyltransferases that synthesize rhamnose-containing glycoconjugates is the current focus amongst the scientific community. In this review, we describe where rhamnose has been found in nature, as well as what is known about TDP-β-l-rhamnose, UDP-β-l-rhamnose, and GDP-α-d-rhamnose biosynthesis. We then focus on examples of rhamnosyltransferases that have been characterized using both in vivo and in vitro approaches from plants and bacteria, highlighting enzymes where 3D structures have been obtained. The ongoing study of rhamnose and rhamnosyltransferases, in particular in pathogenic organisms, is important to inform future drug discovery projects and vaccine development.

AB - Rhamnose is an important 6-deoxy sugar present in many natural products, glycoproteins, and structural polysaccharides. Whilst predominantly found as the l-enantiomer, instances of d-rhamnose are also found in nature, particularly in the Pseudomonads bacteria. Interestingly, rhamnose is notably absent from humans and other animals, which poses unique opportunities for drug discovery targeted towards rhamnose utilizing enzymes from pathogenic bacteria. Whilst the biosynthesis of nucleotide-activated rhamnose (NDP-rhamnose) is well studied, the study of rhamnosyltransferases that synthesize rhamnose-containing glycoconjugates is the current focus amongst the scientific community. In this review, we describe where rhamnose has been found in nature, as well as what is known about TDP-β-l-rhamnose, UDP-β-l-rhamnose, and GDP-α-d-rhamnose biosynthesis. We then focus on examples of rhamnosyltransferases that have been characterized using both in vivo and in vitro approaches from plants and bacteria, highlighting enzymes where 3D structures have been obtained. The ongoing study of rhamnose and rhamnosyltransferases, in particular in pathogenic organisms, is important to inform future drug discovery projects and vaccine development.

KW - biosynthesis

KW - glycoproteins

KW - pathogens

KW - polysaccharides

KW - rhamnose

UR - https://www.scopus.com/pages/publications/85101671855

U2 - 10.1042/BCJ20200505

DO - 10.1042/BCJ20200505

M3 - Review article

C2 - 33599745

SN - 0264-6021

VL - 478

SP - 685

EP - 701

JO - Biochemical Journal

JF - Biochemical Journal

IS - 4

ER -