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Title: A directed-overflow and damage-control N -glycosidase in riboflavin biosynthesis

Plants and bacteria synthesize the essential human micronutrient riboflavin (vitamin B2) via the same multistep pathway. The early intermediates of this pathway are notoriously reactive, and may be overproduced in vivo because riboflavin biosynthesis enzymes lack feedback controls. Here we demonstrate disposal of riboflavin intermediates by COG3236 (DUF1768), a protein of previously unknown function that is fused to two different riboflavin pathway enzymes in plants and bacteria (RIBR and RibA, respectively). We present cheminformatic, biochemical, genetic, and genomic evidence to show that: (i) plant and bacterial COG3236 proteins cleave the N-glycosidic bond of the first two intermediates of riboflavin biosynthesis, yielding relatively innocuous products; (ii) certain COG3236 proteins are in a multienzyme riboflavin biosynthesis complex that gives them privileged access to riboflavin intermediates; and (iii) COG3236 action in Arabidopsis thaliana and Escherichia coli helps maintain flavin levels. We find COG3236 proteins thus illustrate two emerging principles in chemical biology: directed overflow metabolism, in which excess flux is diverted out of a pathway, and the pre-emption of damage from reactive metabolites.
 [1] ;  [2] ;  [1] ;  [3] ;  [1] ;  [4] ;  [5] ;  [6] ;  [6] ;  [6] ;  [2] ;  [5] ;  [7] ;  [8] ;  [1]
  1. Univ. of Florida, Gainesville, FL (United States). Horticultural Sciences Dept.
  2. Univ. of Florida, Gainesville, FL (United States). Food Science and Human Nutrition Dept.
  3. Northwestern Univ., Evanston, IL (United States). Dept. of Chemical and Biological Engineering; Argonne National Lab. (ANL), Argonne, IL (United States). Mathematics and Computer Science Division
  4. Univ. of Florida, Gainesville, FL (United States). McKnight Brain Inst.
  5. Univ. of Florida, Gainesville, FL (United States). Dept. of Biochemistry and Molecular Biology
  6. Washington State Univ., Pullman, WA (United States). Inst. of Biological Chemistry
  7. Argonne National Lab. (ANL), Argonne, IL (United States). Mathematics and Computer Science Division; Univ. of Chicago, IL (United States). Computation Inst.
  8. Univ. of Florida, Gainesville, FL (United States). Dept. of Microbiology and Cell Science
Publication Date:
OSTI Identifier:
Grant/Contract Number:
IOS-1025398; 1U24DK097209-01A1; MCB-1153413; MCB-1153357
Accepted Manuscript
Journal Name:
Biochemical Journal
Additional Journal Information:
Journal Volume: 466; Journal Issue: 1; Journal ID: ISSN 0264-6021
Biochemical Society
Research Org:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE; National Science Foundation (NSF)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES Arabidopsis thaliana; Maillard cascade; metabolite damage; Vibrio vulnificus; vitamin B2; Zea mays