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Title: A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli

Journal Article · · Molecular Microbiology
DOI: https://doi.org/10.1111/mmi.14459 · OSTI ID:1593716
 [1];  [2];  [3];  [4];  [2];  [5]; ORCiD logo [2]
  1. The Ohio State Univ., Columbus, OH (United States); Ohio State University
  2. The Ohio State Univ., Columbus, OH (United States)
  3. Max Planck Inst. for Terrestrial Microbiology, Marburg (Germany)
  4. Donald Danforth Plant Science Center, St. Louis, MO (United States)
  5. Inst. for Genomic Biology, Champaign, IL (United States); Univ. of Illinois at Urbana-Champaign, IL (United States)

S-adenosyl-L-methionine (SAM) is a necessary co-substrate for numerous essential enzymatic reactions including protein and nucleotide methylations, secondary metabolite synthesis, and radical-mediated processes. Radical SAM enzymes produce 5’-deoxyadenosine, and SAM-dependent enzymes for polyamine, neurotransmitter, and quorum sensing compound synthesis produce 5’-methylthioadenosine as byproducts. Both are inhibitory and must be addressed by all cells. This work establishes a bifunctional oxygen-independent salvage pathway for 5’-deoxyadenosine and 5’-methylthioadenosine in both Rhodospirillum rubrum and Extraintestinal Pathogenic Escherichia coli. Homologous genes for this pathway are widespread in bacteria, notably pathogenic strains within several families. A phosphorylase (Rhodospirillum rubrum) or separate nucleoside and kinase (Escherichia coli) followed by an isomerase and aldolase sequentially function to salvage these two wasteful and inhibitory compounds into adenine, dihydroxyacetone phosphate and acetaldehyde or (2-methylthio)acetaldehyde during both aerobic and anaerobic growth. Both SAM byproducts are metabolized with equal affinity during aerobic and anaerobic growth conditions, suggesting that the dual-purpose salvage pathway plays a central role in numerous environments, notably the human body during infection. Finally, our newly discovered bifunctional oxygen-independent pathway, widespread in bacteria, salvages at least two byproducts of SAM-dependent enzymes for carbon and sulfur salvage, contributing to cell growth.

Research Organization:
The Ohio State Univ., Columbus, OH (United States)
Sponsoring Organization:
Deutsche Forschungsgemeinschaft (DFG); National Institutes of Health (NIH); National Science Foundation (NSF); Ohio State University; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
SC0019338
OSTI ID:
1593716
Journal Information:
Molecular Microbiology, Journal Name: Molecular Microbiology Journal Issue: 5 Vol. 113; ISSN 0950-382X
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English

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