Pioneering microbial synthesis of gangliosides in the filamentous fungus Ashbya gossypii
File(s)
Published version
Author(s)
Montero-Bullón, Javier F
Martín-González, Javier
Ledesma-Amaro, Rodrigo
Jiménez, Alberto
Buey, Rubén M
Type
Journal Article
Abstract
Gangliosides are essential glycosphingolipids critical in neurodevelopment and cell signaling. Traditionally sourced from animal tissues, their production raises ethical concerns and faces challenges in scalability and cost. Chemoenzymatic methods have emerged as alternatives but lack flexibility and broad industrial applicability of microbial systems. However, complete microbial biosynthesis remains challenging due to the complexity of reconstructing the biosynthetic pathway in non-native hosts. We report the first successful complete microbial synthesis of gangliosides by engineering the industrial filamentous fungus Ashbya gossypii. Using modular metabolic engineering, we heterologously expressed human and yeast enzymes to reconstruct a functional ganglioside biosynthetic pathway. Pathways for producing activated N-acetylneuraminic acid, lactosylceramide, and sialylated intermediates were integrated, yielding GM3 and GD3 at milligram-per-liter levels. These titers were further enhanced by introducing a heterologous Leloir pathway for galactose metabolism. This work represents a foundational advance in microbial glycoengineering, offering a scalable, animal-free microbial platform for ganglioside production with broad applications.
Date Issued
2025-08-29
Date Acceptance
2025-08-21
Citation
Biotechnology for Biofuels and Bioproducts, 2025, 18
ISSN
2731-3654
Publisher
BMC
Journal / Book Title
Biotechnology for Biofuels and Bioproducts
Volume
18
Copyright Statement
© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40883847
PII: 10.1186/s13068-025-02697-4
Subjects
Ashbya gossypii
Gangliosides
Metabolic engineering
Sphingolipids
Publication Status
Published
Coverage Spatial
England
Article Number
95
Date Publish Online
2025-08-29