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

Journal Article · · Biochemical Journal
DOI:https://doi.org/10.1042/bj20141237· OSTI ID:1280875
 [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

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE; National Science Foundation (NSF)
Grant/Contract Number:
IOS-1025398; 1U24DK097209-01A1; MCB-1153413; MCB-1153357
OSTI ID:
1280875
Journal Information:
Biochemical Journal, Vol. 466, Issue 1; ISSN 0264-6021
Publisher:
Biochemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 34 works
Citation information provided by
Web of Science

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Cited By (10)

Novel Stenotrophomonas maltophilia temperate phage DLP4 is capable of lysogenic conversion journal April 2019
Maize Dek33 encodes a pyrimidine reductase in riboflavin biosynthesis that is essential for oil-body formation and ABA biosynthesis during seed development journal June 2019
Systematic identification and analysis of frequent gene fusion events in metabolic pathways journal June 2016
Identification and characterization of the missing phosphatase on the riboflavin biosynthesis pathway in Arabidopsis thaliana journal September 2016
Differential regulation of riboflavin supply genes in Vibrio cholerae journal February 2017
Contribution of riboflavin supply pathways to Vibrio cholerae in different environments journal November 2017
MINEs: open access databases of computationally predicted enzyme promiscuity products for untargeted metabolomics journal August 2015
Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity journal July 2016
Transcriptomics reveals a cross-modulatory effect between riboflavin and iron and outlines responses to riboflavin biosynthesis and uptake in Vibrio cholerae journal February 2018
Optimization of an Ultrasound-Assisted Extraction for Simultaneous Determination of Antioxidants in Sesame with Response Surface Methodology journal August 2019

Figures / Tables (6)


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