Novel substrate specificities of two lacto-N-biosidases towards β-linked galacto-N-biose-containing oligosaccharides of globo H, Gb5, and GA1

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.

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“…. In addition, LnbX can also release a modified and unmodified GNB unit from globo-series glycosphingolipids (Gotoh et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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

Yamada

Gotoh

Sakanaka

et al. 2017

Cell Chemical Biology

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107

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“…1; Sakurama et al, 2013). LnbX can act not only on LNT, but also on human-derived glycoconjugate sugars (Gotoh et al, 2015). We demonstrated that LnbX + ÀB.…”

Section: Case Studiesmentioning

confidence: 75%

“…; Sakurama et al ., ). LnbX can act not only on LNT, but also on human‐derived glycoconjugate sugars (Gotoh et al ., ). We demonstrated that LnbX + − B. longum strains promote the growth of other bifidobacteria through cross‐feeding of LNT by‐products when co‐cultured in medium containing LNT as a carbon source.…”

Section: Case Studiesmentioning

confidence: 97%

Minority species influences microbiota formation: the role of Bifidobacterium with extracellular glycosidases in bifidus flora formation in breastfed infant guts

Gotoh

Ojima

Katayama

2019

Microbial Biotechnology

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Summary The human body houses a variety of microbial ecosystems, such as the microbiotas on the skin, in the oral cavity and in the digestive tract. The gut microbiota is one such ecosystem that contains trillions of bacteria, and it is well established that it can significantly influence host health and diseases. With the advancement in bioinformatics tools, numerous comparative studies based on 16S ribosomal RNA ( rRNA ) gene sequences, metabolomics, pathological and epidemical analyses have revealed the correlative relationship between the abundance of certain taxa and disease states or amount of certain causative bioactive compounds. However, the 16S rRNA ‐based taxonomic analyses using next‐generation sequencing ( NGS ) technology essentially detect only the majority species. Although the entire gut microbiome consists of 10 13 microbial cells, NGS read counts are given in multiples of 10 6 , making it difficult to determine the diversity of the entire microbiota. Some recent studies have reported instances where certain minority species play a critical role in creating locally stable conditions for other species by stabilizing the fundamental microbiota, despite their low abundance. These minority species act as ‘keystone species’, which is a species whose effect on the community is disproportionately large compared to its relative abundance. One of the attributes of keystone species within the gut microbiota is its extensive enzymatic capacity for substrates that are rare or difficult to degrade for other species, such as dietary fibres or host‐derived complex glycans, like human milk oligosaccharides ( HMO s). In this paper, we propose that more emphasis should be placed on minority taxa and their possible role as keystone species in gut microbiota studies by referring to our recent studies on HMO ‐mediated microbiota formation in the infant gut.

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“…21 Thus we analysed the conformations of the pyranose ring containing inhibitors 2, 4 and 5 in detail using the Cremer-Pople system which is used to determine the conformation of six-membered rings (see table in ESI †). 40 The authors wish to thank the Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, which is supported by University, State and Federal Government funding. 36 This conformation is also close to the putative transition states in the proposed conformational itinerary of the pyranose ring for BbLNBase 16 and other enzymes that utilize a substrate-assisted catalytic mechanism.…”

mentioning

confidence: 99%

Gaining insight into the catalysis by GH20 lacto-N-biosidase using small molecule inhibitors and structural analysis

et al. 2015

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Novel substrate specificities of two lacto-N-biosidases towards β-linked galacto-N-biose-containing oligosaccharides of globo H, Gb5, and GA1

Cited by 17 publications

References 49 publications

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

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

Minority species influences microbiota formation: the role of Bifidobacterium with extracellular glycosidases in bifidus flora formation in breastfed infant guts

Gaining insight into the catalysis by GH20 lacto-N-biosidase using small molecule inhibitors and structural analysis

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