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Biochem J. 2015 Feb 15;466(1):137-45. doi: 10.1042/BJ20141237.

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

Author information

1
*Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
2
†Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, U.S.A.
3
‡Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, U.S.A.
4
║AMRIS Facility, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, U.S.A.
5
¶Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, U.S.A.
6
**Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
7
§Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL 60439, U.S.A.
8
‡‡Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, U.S.A.

Abstract

Plants and bacteria synthesize the essential human micronutrient riboflavin (vitamin B2) via the same multi-step pathway. The early intermediates of this pathway are notoriously reactive and may be overproduced in vivo because riboflavin biosynthesis enzymes lack feedback controls. In the present paper, 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 multi-enzyme 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. 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.

PMID:
25431972
PMCID:
PMC4477702
DOI:
10.1042/BJ20141237
[Indexed for MEDLINE]
Free PMC Article

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