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Cell Chem Biol. 2017 Apr 20;24(4):515-524.e5. doi: 10.1016/j.chembiol.2017.03.012. Epub 2017 Apr 6.

Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum.

Author information

1
Department of Biotechnology, The University of Tokyo, Tokyo 113-8657, Japan; Graduate School of Biostudies, Kyoto University, Kyoto 606-8052, Japan.
2
Graduate School of Biostudies, Kyoto University, Kyoto 606-8052, Japan.
3
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Ishikawa 921-8836, Japan.
4
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
5
School of Human Cultures, The University of Shiga Prefecture, Hikone, Shiga 522-8533, Japan.
6
Department of Biotechnology, The University of Tokyo, Tokyo 113-8657, Japan.
7
Food Research Institute, National Agriculture and Food Research Organization, Ibaraki 305-8642, Japan.
8
Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
9
Graduate School of Biostudies, Kyoto University, Kyoto 606-8052, Japan; Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Ishikawa 921-8836, Japan. Electronic address: takane@lif.kyoto-u.ac.jp.
10
Department of Biotechnology, The University of Tokyo, Tokyo 113-8657, Japan. Electronic address: asfushi@mail.ecc.u-tokyo.ac.jp.

Abstract

Breast-fed infants generally have a bifidobacteria-rich microbiota with recent studies indicating that human milk oligosaccharides (HMOs) selectively promote bifidobacterial growth. Bifidobacterium bifidum possesses a glycoside hydrolase family 20 lacto-N-biosidase for liberating lacto-N-biose I from lacto-N-tetraose, an abundant HMO unique to human milk, while Bifidobacterium longum subsp. longum has a non-classified enzyme (LnbX). Here, we determined the crystal structure of the catalytic domain of LnbX and provide evidence for creation of a novel glycoside hydrolase family, GH136. The structure, in combination with inhibition and mutation studies, provides insight into the molecular mechanism and broader substrate specificity of this enzyme. Moreover, through genetic studies, we show that lnbX is indispensable for B. longum growth on lacto-N-tetraose and is a key genetic factor for persistence in the gut of breast-fed infants. Overall, this study reveals possible evolutionary routes for the emergence of symbiosis between humans and bifidobacterial species in the infant gut.

KEYWORDS:

X-ray crystallography; bifidobacteria; glycoside hydrolase; human microbe co-evolution; human microbe symbiosis; human milk oligosaccharides; infant gut microbiota; inhibitors; lacto-N-biosidase; lacto-N-tetraose

PMID:
28392148
DOI:
10.1016/j.chembiol.2017.03.012
[Indexed for MEDLINE]
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