Biochemical production from sustainable carbon sources by Komagataella phaffii

Abstract

The use of sustainable carbon sources (SCSs) for biochemical production is needed to facilitate the chemical process industries transition towards the net-zero age and greener economy. The use of SCSs such as crude glycerol, ethanol, methanol, acetate, lactate, and formate offers potential cost reduction and sustainability benefits. However, the integration of SCSs into bioindustries is generally challenged by their low uptake rates, toxicity, and the metabolic stress they exert. Therefore, their transport rates from fermentation medium into the cell and then sequential intracellular reaction rates towards target products need to be fine-tuned. This review begins with the importance of use of SCSs in biochemical process industries and continues with the current state of metabolic engineering strategies employed to optimize biochemical and recombinant protein production. In turn, metabolic engineering strategies to increase the uptake rates of two SCSs, ethanol and acetate, and the carbon fluxes fueling the TCA cycle in Komagataella phaffii (Pichia pastoris) are discussed. Moreover, the latest findings on bioreactor operation condition optimization are compiled with a special emphasis on recombinant protein production. We conclude that the future of K. phaffii-based bioprocessing lies in integrating metabolic and bioreactor engineering with systems biology, while advances in synthetic biology, such as modular genome editing and machine learning for promoter and pathway design, will further refine the metabolic versatility of K. phaffii.