4.6 Review

Advances in Cell Engineering of the Komagataella phaffii Platform for Recombinant Protein Production

Journal

METABOLITES
Volume 12, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/metabo12040346

Keywords

Komagataella phaffii; Pichia pastoris; recombinant protein; cell engineering; metabolic engineering

Funding

  1. FONDECYT Regular grant-Agencia Nacional de Investigacion y Desarrollo (ANID), Chile [1191196]
  2. FONDECYT Iniciacion grant-Agencia Nacional de Investigacion y Desarrollo (ANID), Chile [11200933]
  3. ANILLO Regular de Ciencia y Tecnologia grant-Agencia Nacional de Investigacion y Desarrollo (ANID), Chile [ACT210068]
  4. Becas Doctorado Nacional grant-Agencia Nacional de Investigacion y Desarrollo (ANID), Chile [21191422, 21211138, 21211233]
  5. Wallonie-Bruxelles International through the Cooperation bilateral Belgique-Chili project [SUB/2019/435787]

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Komagataella phaffii has become an important microorganism for recombinant protein production, particularly in industrial settings. Significant progress has been made in improving recombinant protein productivity and reducing production costs. Cell engineering approaches, including metabolic engineering, transcription factor modulation, and manipulation of protein folding and secretion pathways, have shown promising results. However, more research is needed in optimizing cultivation parameters in larger-scale bioreactors.
Komagataella phaffii (formerly known as Pichia pastoris) has become an increasingly important microorganism for recombinant protein production. This yeast species has gained high interest in an industrial setting for the production of a wide range of proteins, including enzymes and biopharmaceuticals. During the last decades, relevant bioprocess progress has been achieved in order to increase recombinant protein productivity and to reduce production costs. More recently, the improvement of cell features and performance has also been considered for this aim, and promising strategies with a direct and substantial impact on protein productivity have been reported. In this review, cell engineering approaches including metabolic engineering and energy supply, transcription factor modulation, and manipulation of routes involved in folding and secretion of recombinant protein are discussed. A lack of studies performed at the higher-scale bioreactor involving optimisation of cultivation parameters is also evidenced, which highlights new research aims to be considered.

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