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Analysis of Fucosylated Human Milk Trisaccharides in Biotechnological Context Using Genetically Encoded Biosensors

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Published on: April 13, 2019

Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multi-omics integration.

Benjamin P Kellman^1,2,3, Anne Richelle¹, Jeong-Yeh Yang⁴

¹Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.

Nature Communications

|May 4, 2022

Summary

Human Milk Oligosaccharides (HMOs) are vital for infant health. This study reveals the molecular pathways of HMO biosynthesis, identifying key genes and enzymes involved in their production.

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Published on: June 20, 2010

Area of Science:

Biochemistry
Systems Biology
Human Lactation

Background:

Human Milk Oligosaccharides (HMOs) are crucial bioactive carbohydrates for infant development.
The precise mechanisms of HMO biosynthesis within the mammary gland are not fully understood.
Existing knowledge gaps hinder targeted research and applications for improving infant health.

Purpose of the Study:

To elucidate the molecular basis of Human Milk Oligosaccharide biosynthesis.
To construct a comprehensive HMO biosynthetic network using integrated data.
To identify novel candidate genes and enzymes responsible for HMO synthesis.

Main Methods:

Integrated systems biology approach combining glycan and RNA expression data.
Development of computational models for major HMO synthesis pathways (>95% of content).
Network analysis to predict gene-enzyme relationships for HMO synthesis reactions.

Main Results:

Successfully reconstructed a significant portion of the HMO biosynthetic network.
Identified candidate genes involved in HMO elongation, branching, fucosylation, and sialylation.
Validated model accuracy by recovering known gene-enzyme relationships and proposing novel candidates consistent with literature.

Conclusions:

Established a foundational molecular understanding of HMO biosynthesis.
Provided a predictive framework for identifying genes and enzymes in HMO synthesis.
Paved the way for advancements in HMO research, applications, and infant health improvement.