ArticleMicrobial cell factories2025
Rewiring central metabolism in Komagataella phaffii for efficient mannose synthesis.
Article in Microbial cell factories, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMannose has wide-ranging applications but microbial fermentation remains underdeveloped compared to biotransformation for its production. The yeast Komagataella phaffii stands out as a premier synthetic biology platform, renowned for its safety profile and exceptional suitability for high-density fermentation. This established chassis organism is ideally positioned for large-scale mannose production through targeted rewiring of its mannose biosynthetic pathway via metabolic engineering.
resultsK. phaffii was metabolically engineered for efficient mannose production using a dual carbon source system: glycerol for biomass generation and glucose for mannose synthesis. To redirect carbon flux toward fructose-6-phosphate (F6P) accumulation at the glycolytic node, glycolytic flux was attenuated by knocking out the phosphofructokinase II (pfk2) gene and downregulating phosphofructokinase I (pfk1). Simultaneously, pentose phosphate pathway flux was reduced by downregulating glucose-6-phosphate dehydrogenase (zwf1). To enhance mannose biosynthesis, conversion of F6P into mannose was promoted by suppressing phosphomannose isomerase (PAS_chr3_1115) and overexpressing the Escherichia coli-derived phosphatase gene yniC. Additionally, three genes involved in arabinitol and ribitol production (PAS_chr2-2_0019, PAS_chr4_0754, and PAS_chr4_0988) were deleted to suppress byproduct accumulation. The engineered strain achieved ~ 121.1 g/L mannose in high-cell-density, fed-batch fermentation, representing the highest reported titer via microbial fermentation to date.
conclusionsThis study achieved efficient mannose production in K. phaffii by remodeling central metabolism. It not only offers a new route for mannose biosynthesis but also establishes a model framework for engineering K. phaffii to produce other high-value bioactive compounds.
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