Title: Oxidative Pathways of Deoxyribose and Deoxyribonate Catabolism

Abstract

ABSTRACT Using genome-wide mutant fitness assays in diverse bacteria, we identified novel oxidative pathways for the catabolism of 2-deoxy-d-ribose and 2-deoxy-d-ribonate. We propose that deoxyribose is oxidized to deoxyribonate, oxidized to ketodeoxyribonate, and cleaved to acetyl coenzyme A (acetyl-CoA) and glyceryl-CoA. We have genetic evidence for this pathway in three genera of bacteria, and we confirmed the oxidation of deoxyribose to ketodeoxyribonatein vitro. InPseudomonas simiae, the expression of enzymes in the pathway is induced by deoxyribose or deoxyribonate, while inParaburkholderia bryophilaand inBurkholderia phytofirmans, the pathway proceeds in parallel with the known deoxyribose 5-phosphate aldolase pathway. We identified another oxidative pathway for the catabolism of deoxyribonate, with acyl-CoA intermediates, inKlebsiella michiganensis. Of these four bacteria, onlyP. simiaerelies entirely on an oxidative pathway to consume deoxyribose. The deoxyribose dehydrogenase ofP. simiaeis either nonspecific or evolved recently, as this enzyme is very similar to a novel vanillin dehydrogenase fromPseudomonas putidathat we identified. So, we propose that these oxidative pathways evolved primarily to consume deoxyribonate, which is a waste product of metabolism. IMPORTANCEDeoxyribose is one of the building blocks of DNA and is released when cells die and their DNA degrades. We identified a bacterium that can grow with deoxyribose as its sole sourcemore » of carbon even though its genome does not contain any of the known genes for breaking down deoxyribose. By growing many mutants of this bacterium together on deoxyribose and using DNA sequencing to measure the change in the mutants’ abundance, we identified multiple protein-coding genes that are required for growth on deoxyribose. Based on the similarity of these proteins to enzymes of known function, we propose a 6-step pathway in which deoxyribose is oxidized and then cleaved. Diverse bacteria use a portion of this pathway to break down a related compound, deoxyribonate, which is a waste product of metabolism. Our study illustrates the utility of large-scale bacterial genetics to identify previously unknown metabolic pathways.« less

Authors:

Price, Morgan N.  ^[1];

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Ray, Jayashree ^[1]; Iavarone, Anthony T. ^[2]; Carlson, Hans K. ^[1]; Ryan, Elizabeth M. ^[3]; Malmstrom, Rex R. ^[3]; Arkin, Adam P. ^[4]; Deutschbauer, Adam M. ^[5]; Rabaey, ed., Korneel

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+ Show Author Affiliations

1. Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA
2. QB3/Chemistry Mass Spectrometry Facility, University of California, Berkeley, California, USA
3. DOE Joint Genome Institute, Walnut Creek, California, USA
4. Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA, Department of Bioengineering, University of California, Berkeley, California, USA
5. Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA, Department of Plant and Microbial Biology, University of California, Berkeley, California, USA

Publication Date:

2019-02-26

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER)

OSTI Identifier:

1493373

Alternate Identifier(s):

OSTI ID: 1508059

Grant/Contract Number:  

AC02-05CH11231

Resource Type:

Published Article

Journal Name:

mSystems

Additional Journal Information:

Journal Name: mSystems Journal Volume: 4 Journal Issue: 1; Journal ID: ISSN 2379-5077

Publisher:

American Society for Microbiology

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; deoxyribonate catabolism; deoxyribose catabolism; high-throughput genetics