Transcriptional regulation of carbohydrate utilization pathways in the Bifidobacterium genus

Khoroshkin, Matvei S.; Leyn, Semen A.; van Sinderen, Douwe; Rodionov., Dmitry A.

Transcriptional regulation of carbohydrate utilization pathways in the Bifidobacterium genus

dc.contributor.author	Khoroshkin, Matvei S.
dc.contributor.author	Leyn, Semen A.
dc.contributor.author	van Sinderen, Douwe
dc.contributor.author	Rodionov., Dmitry A.
dc.contributor.funder	Russian Science Foundation	en
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	National Institutes of Health	en
dc.date.accessioned	2017-02-23T15:46:38Z
dc.date.available	2017-02-23T15:46:38Z
dc.date.issued	2016-02-09
dc.date.updated	2017-02-23T15:27:27Z
dc.description.abstract	Bifidobacteria, which represent common commensals of mammalian gut, are believed to have positive effects on human health. The influence of certain non-digestible carbohydrates (and their use as so-called prebiotics) on growth and metabolic activity of bifidobacteria is of increasing interest; however, mechanisms of transcriptional control of carbohydrate metabolism are poorly understood in these species. We used a comparative genomics approach to reconstruct carbohydrate utilization pathways and transcriptional regulons in 10 Bifidobacterium genomes. Analysis of regulatory gene regions revealed candidate DNA motifs and reconstructed regulons for 268 transcription factors from the LacI, ROK, DeoR, AraC, GntR, and TetR families that form 64 orthologous groups of regulators. Most of the reconstructed regulons are local and control specific catabolic pathways for host- and diet-derived glycans and monosaccharides. Mosaic distributions of many of these local regulators across Bifidobacterium species correlate with distribution of corresponding catabolic pathways. In contrast, the maltose, galactose, sucrose, and fructose regulons, as well as a novel global LacI-family regulator that is predicted to control the central carbohydrate metabolism and arabinose catabolism genes, are universally present in all 10 studied bifidobacteria. A novel group of TetR-family regulators presumably controls the glucoside and galactoside utilization pathways. Paralogs of the ribose repressor RbsR control the pyrimidine nucleoside utilization genes. Multiple paralogs of the maltose regulator MalR co-regulate large sets of genes involved in maltodextrin utilization. The inferred metabolic regulons provide new insights on diverse carbohydrate utilization networks in bifidobacteria that can be employed in metabolic modeling, phenotype prediction and the rational development of novel prebiotics.	en
dc.description.sponsorship	Russian Science Foundation (grant number 14-14-00289); National Institute of Health (grant number GM108527); Science Foundation Ireland (through the Irish Government’s National Development Plan (Grant number SFI/12/RC/2273))	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Khoroshkin, M. S., Leyn, S. A., Van Sinderen, D. and Rodionov, D. A. (2016) 'Transcriptional Regulation of Carbohydrate Utilization Pathways in the Bifidobacterium Genus', Frontiers in Microbiology, 7(120). doi:10.3389/fmicb.2016.00120	en
dc.identifier.doi	10.3389/fmicb.2016.00120
dc.identifier.endpage	120-14	en
dc.identifier.issn	1664-302X
dc.identifier.journaltitle	Frontiers In Microbiology	en
dc.identifier.startpage	120-1	en
dc.identifier.uri	https://hdl.handle.net/10468/3680
dc.identifier.volume	7	en
dc.language.iso	en	en
dc.publisher	Frontiers Media	en
dc.rights	© 2016 Khoroshkin, Leyn, Van Sinderen and Rodionov. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	en
dc.subject	Carbohydrate metabolism	en
dc.subject	Sugar catabolism	en
dc.subject	Transcription factors	en
dc.subject	Regulatory networks	en
dc.subject	Regulatory sequences	en
dc.subject	Nucleic acid	en
dc.subject	Bifidobacteria	en
dc.subject	Comparative genomics	en
dc.title	Transcriptional regulation of carbohydrate utilization pathways in the Bifidobacterium genus	en
dc.type	Article (peer-reviewed)	en