Metabolic engineering of Komagataella phaffii for enhanced production of heterologous proteins and small molecules: key strategies and future directions.

Authors

Jiaoyu Xin, Lu Zhao, Youxin Meng, Ziye Tian, Kaikai Lv, Chenyu Xue, Na Dong

Published in

Applied and environmental microbiology. Volume 92. Issue 8. Pages e0011026. Aug 19, 2026. Epub Jul 16, 2026.

Abstract

Komagataella phaffii (syn. Pichia pastoris) is an important host for the production of recombinant proteins and small molecules, often exhibiting superior performance compared to other heterologous hosts. With advancements in synthetic biology and computational biology, metabolic engineering has become a key strategy for achieving high-level heterologous proteins and small molecules in K. phaffii for industrial and commercial applications. In this review, we provide an overview of advances in K. phaffii metabolic engineering. We first discuss the development of the K. phaffii expression system. Subsequently, we analyze core optimization strategies, including metabolic flux control, metabolic dynamic control, application of system modeling, chassis cell optimization, and recombinant protein and small-molecule production, before finally summarizing the current challenges and future development directions.

PMID:
42461011
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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