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Elucidating the biosynthetic pathways of human milk oligosaccharides through a systems biology approach
Author(s) -
Lewis Nathan E.,
Richelle Anne E.,
Kellman Benjamin E.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05286
Subject(s) - context (archaeology) , glycosyltransferase , computational biology , transcriptome , biology , enzyme , biosynthesis , metabolic pathway , human health , biochemistry , bioinformatics , medicine , gene , gene expression , environmental health , paleontology
Human Milk Oligosaccharides (HMOs) are abundant and functionally important components of milk, with major impacts on the health and development of the breastfed infant. Despite their discovery more than half a century ago, their biosynthesis in the human mammary gland remains incompletely characterized. To address this we have developed a framework for predicting glycosyltransferases responsible for synthesizing HMOs and the structures of poorly characterized HMOs. This approach builds nearly 49 million possible pathway maps that could synthesize the 16 most abundant HMOs. From this, we identified the most likely pathways, enzymes, and HMO structures when analyzing the pathway maps in the context of transcriptomic data and HMO measurements from two cohorts of women. We subsequently validated the predicted enzymes through assays. Through this we were able to unravel the molecular basis for HMO biosynthesis including enzymes responsible, and therefore this knowledge can now be used to guide new strategies for HMO synthesis for academic and nutritional use.