The industrial yeast Komagataella phaffii blooms for advanced biomanufacturing

The industrial yeast Komagataella phaffii is emerging as a versatile chassis for advanced biomanufacturing. This review systematically summarizes recent progress in development and expanding applications of K. phaffii in addition to its traditional role in recombinant protein expression. This yeast demonstrates great potential as a sustainable source of single cell protein and a dominant host for bulk recombinant protein production in the fields of food, feed, biomaterial, biopharmaceutical, and industrial enzyme. Beyond protein expression, it has shown promising capabilities in the biosynthesis of diverse natural products, including flavonoids, alkaloids, terpenoids, polyketides, etc.. Its flexible metabolic network enables utilization of sustainable C1 and C2 substrates, supporting low-carbon and sustainable bioeconomy oriented biomanufacturing. These advances are underpinned by substantial innovations in genetic toolboxes, particularly CRISPR-based genome editing, synthetic promoter engineering, programmable expression systems, and genome-scale metabolic modeling, which have markedly enhanced the precision and efficiency of strain engineering. Despite these advantages, challenges remain in achieving ultra-high protein titers, developing humanized glycosylation strategies for food applications, improving cellular stress tolerance, and improving synthesis of toxic natural products. Addressing these limitations through integrated metabolic engineering and systems biology approaches will be critical to make K. phaffii a next-generation industrial workhorse for advanced biomanufacturing.