The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars

Abstract

Carbohydrates serve many structural and functional roles in biology. While the majority of monosaccharides are characterized by the chemical composition (CH2O)n, modifications including deoxygenation, C-alkylation, amination, O- and N-methylation, which are characteristic of many sugar appendages of secondary metabolites, are not uncommon. Interestingly, some sugar molecules are formed via modifications including amine oxidation, sulfur incorporation, and "high-carbon" chain attachment. Most of these unusual sugars have been identified over the past several decades as components of microbially produced natural products, although a few high-carbon sugars are also found in the lipooligosaccharides of the outer cell walls of Gram-negative bacteria. Despite their broad distribution in nature, these sugars are considered "rare" due to their relative scarcity. The biosynthetic steps that underlie their formation continue to perplex researchers to this day and many questions regarding key transformations remain unanswered. This review will focus on our current understanding of the biosynthesis of unusual sugars bearing oxidized amine substituents, thio-functional groups, and high-carbon chains.

Scheme 1

Proposed pathway for the biosynthesis of hydroxyaminosugar

Scheme 2

Proposed pathways for the biosynthesis of nitrosugars

Scheme 3

Reactions catalyzed by N-oxygenases

Scheme 4

Proposed mechanism for ORF36-catalyzed N-oxidation

Scheme 5

Possible mechanism of sulfur incorporation into albomycin catalyzed by radical SAM dependent enzymes

Scheme 6

ThiG-catalyzed thiazol formation

Scheme 7

Biosynthesis of 2-thioglucose in BE-7585A

Scheme 8

Possible mechanism for the formation of the thioether linkage in BE-7585 A

Scheme 9

Proposed biosynthesis of 2-thioglucose in rhodonocardin

Scheme 10

Proposed pathway for the biosynthesis of 4-thioglucose in calicheamicin

Scheme 11

Proposed pathway for the biosynthesis of glucosinolates

Scheme 12

Proposed pathway for the biosynthesis of sulfoquinovosyl diacylglycerol

Scheme 13

Proposed pathways for the biosynthesis of the tunicamine core

Scheme 14

Proposed biosynthesis of 5′-C-glycyluridine core

Scheme 15

Proposed pathways for the biosynthesis of octosyl acids, polyoxins and nikkomycins

Scheme 16

Proposed pathway for the biosynthesis of mildiomycin

Scheme 17

Proposed biosynthetic precursors for griseolic acid A

Scheme 18

Proposed biosynthetic precursors for sinefungin (A9145)

Scheme 19

Reactions catalyzed by LmbR and LmbN in the biosynthesis of MTL

Scheme 20

Proposed pathways for the biosynthesis of 4-thioheptouronic acid in albomycin

Scheme 21

Proposed pathway for the biosynthesis of bicyclic octose moiety in apramycin

Scheme 22

Biosynthetic pathways for NeuNAc and KDO

Scheme 23

Proposed pathway for the biosynthesis of yersiniose and mechanism of YerE