Biosynthetic enzymes of unusual microbial sugars

Abstract

The biological importance of proteins and nucleic acids in the natural world is undeniable, and research efforts on these macromolecules have often overshadowed those directed at carbohydrates. It is now known, however, that carbohydrates not only play roles in energy storage and plant cell wall structure, but are also intimately involved in such processes as fertilization, the immune response, and cell adhesion. Indeed, recent years have seen an explosion in research efforts directed at uncovering and understanding new sugar moieties. The dideoxysugars and trideoxysugars, which are synthesized by a variety of bacteria, fungi, and plants, represent an especially intriguing class of carbohydrates. They are found, for example, on the lipopolysaccharides of some Gram-negative bacteria or on antibacterial agents such as erythromycin. Many of them are formed from simple monosaccharides such as glucose-6-phosphate or fructose-6-phosphate via a myriad of enzymatic reactions including acetylations, aminations, dehydrations, epimerizations, reductions, and methylations. In this review we focus on the recent structural investigations of the bacterial N-acetyltransferases and the PLP-dependent aminotransferases that function on nucleotide-linked sugar substrates.

Figure 1

Examples of di- and trideoxysugars produced by microbial sources.

Figure 2

The structure of PglD. A ribbon representation of the PglD trimer is depicted in (a) with the CoA ligands drawn as sticks (PDB code 2VHE [8]). A stereo view of an individual subunit is presented in (b). Shown in (c) are the positions of acetyl-CoA and the UDP-4’-amino sugar substrate when bound in the PglD active site (PDB codes 3BSY and 3BSS [9]). The active site is formed between two subunits as colored in salmon and light blue. The black dashed lines represent possible hydrogen bonding interactions, whereas the green dashed line indicates the direction of attack at the carbonyl carbon of acetyl-CoA by the sugar amino group.

Figure 3

Differences in NDP-sugar binding between PglD and QdtC. The ribbon representation shown is that for QdtC. The carbon atoms for the acetyl-CoA and UDP-QuiNAc4N ligands, when bound to PglD, are highlighted in blue whereas those for the CoA and dTDP-Quip3N ligands, when anchored to QdtC, are displayed in black.

Figure 4

The structure of the ArnB dimer. The two subunits are highlighted in light blue and light green and the PLP cofactors are depicted in space-filling representations.

Figure 5

Reactions catalyzed by ColD and GDP-perosamine synthase.