Oxidative Pathways of Deoxyribose and Deoxyribonate Catabolism

Journal Article · 05 February 2019 · mSystems

DOI: https://doi.org/10.1128/msystems.00297-18 · OSTI ID:1493373

Price, Morgan N.  ^[1]; 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. ^[4]; Rabaey, Korneel ^[5]

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1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
2. Univ. of California, Berkeley, CA (United States)
3. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
5. Ghent Univ. (Belgium)

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 source 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.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 1493373
• Alternate ID(s): OSTI ID: 1508059
• Journal Information: mSystems, Vol. 4, Issue 1; ISSN 2379-5077
• Publisher: American Society for MicrobiologyCopyright Statement
• Country of Publication: United States
• Language: English