Salvage of the 5-deoxyribose byproduct of radical SAM enzymes

Guillaume A W Beaudoin,Jacob Folz,Oliver Fiehn,Alexander Angerhofer,Steven D Bruner,Andrew D Hanson,Qiang Li,Justin L Goodsell

doi:10.1038/s41467-018-05589-4

Abstract

5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine (SAM) enzymes. The degradative fate of 5-deoxyribose is unknown. Here, we define a salvage pathway for 5-deoxyribose in bacteria, consisting of phosphorylation, isomerization, and aldol cleavage steps. Analysis of bacterial genomes uncovers widespread, unassigned three-gene clusters specifying a putative kinase, isomerase, and sugar phosphate aldolase. We show that the enzymes encoded by the Bacillus thuringiensis cluster, acting together in vitro, convert 5-deoxyribose successively to 5-deoxyribose 1-phosphate, 5-deoxyribulose 1-phosphate, and dihydroxyacetone phosphate plus acetaldehyde. Deleting the isomerase decreases the 5-deoxyribulose 1-phosphate pool size, and deleting either the isomerase or the aldolase increases susceptibility to 5-deoxyribose. The substrate preference of the aldolase is unique among family members, and the X-ray structure reveals an unusual manganese-dependent enzyme. This work defines a salvage pathway for 5-deoxyribose, a near-universal metabolite.

Highlights

5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine (SAM) enzymes
It has been proposed that the archaeon Methanocaldococcus jannaschii metabolizes dAdo using enzymes similar to the 5′methylthioadenosine phosphorylase and 5-methylthioribose 1phosphate isomerase of the methionine salvage pathway, and that the 5-deoxyribulose 1-phosphate so formed is converted to the aromatic amino acid precursor 6′-deoxy-5-ketofructose 1phosphate[9]
The reaction sequence (Fig. 1a) would be analogous to the catabolic pathways of the 6-deoxyhexoses L-fucose and L-rhamnose in E. coli, which proceed through isomerase, kinase, and class II aldolase steps to give dihydroxyacetone phosphate (DHAP) and lactaldehyde[10,11] (Supplementary Fig. 1a), and to the metabolism of 5′fluorodeoxyadenosine to DHAP and fluoroacetaldehyde in Streptomyces cattleya[12] (Supplementary Fig. 1b)

Summary

Introduction

5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine (SAM) enzymes. Radical S-adenosyl-L-methionine (SAM) enzymes occur in all domains of life and catalyze diverse reactions via the generation of highly reactive 5′-deoxyadenosyl radicals[1] These enzymes function in key pathways that include the biosynthesis of thiamin, biotin, lipoate, and molybdopterin[1,2]. It has been shown in rats that dR1P is dephosphorylated and reduced to 5-deoxyribitol, which is excreted[8] Because such excretion wastes a potentially valuable sugar, other disposal pathways that salvage 5-deoxyribose by recycling it to mainstream metabolites seem likely a priori to exist in nature. It has been proposed that the archaeon Methanocaldococcus jannaschii metabolizes dAdo using enzymes similar to the 5′methylthioadenosine phosphorylase and 5-methylthioribose 1phosphate isomerase of the methionine salvage pathway, and that the 5-deoxyribulose 1-phosphate (dRu1P) so formed is converted to the aromatic amino acid precursor 6′-deoxy-5-ketofructose 1phosphate[9]. This work establishes a salvage pathway for disposal of 5-deoxyribose, a near-universal metabolite

Methods

Results

Conclusion