Advances in Komagataella phaffii Engineering for the Production of Renewable Chemicals and Proteins

Abstract

The need for a more sustainable society has prompted the development of bio-based processes to produce fuels, chemicals, and materials in substitution for fossil-based ones. In this context, microorganisms have been employed to convert renewable carbon sources into various products. The methylotrophic yeast Komagataella phaffii has been extensively used in the production of heterologous proteins. More recently, it has been explored as a host organism to produce various chemicals through new metabolic engineering and synthetic biology tools. This review first summarizes Komagataella taxonomy and diversity and then highlights the recent approaches in cell engineering to produce renewable chemicals and proteins. Finally, strategies to optimize and develop new fermentative processes using K. phaffii as a cell factory are presented and discussed. The yeast K. phaffii shows an outstanding performance for renewable chemicals and protein production due to its ability to metabolize different carbon sources and the availability of engineering tools. Indeed, it has been employed in producing alcohols, carboxylic acids, proteins, and other compounds using different carbon sources, including glycerol, glucose, xylose, methanol, and even CO2.

Single carbon metabolism – A new paradigm for microbial bioprocesses?

“…Research continued in different directions. Yeasts like Komagataella phaffii [ 19 , 20 ] and Ogataea polymorpha [ 21 ] were developed into production hosts for recombinant proteins when it was found that their alcohol oxidase genes were controlled by very strong and highly regulated promoters [ 22 , 23 ]. The success of these applications initiated further research on the fundamentals of methanol metabolism in these yeasts, leading to novel concepts of metabolic engineering to enhance productivity and carbon yield, or even expand the substrate spectrum [ [24] , [25] , [26] ].…”

Precision Fermentation as an Alternative to Animal Protein, a Review

“…Its efficiency, cost-effectiveness, and high productivity make this yeast a popular choice for the production of eukaryotic proteins [40]. K. phaffii is also notable for its ability to achieve high cell densities and, consequently, increased protein yield, in addition to not secreting many proteins inherent to it, which simplifies the downstream process [50][51][52][53][54][55]. Other yeasts such as Saccharomyces cerevisiae, Yarrowia lipolytica, and Kluyveromyces marxianus are also employed as models for the industrial production of enzymes and food ingredients [39,56].…”

Study of pH and Thermodynamic Parameters via Circular Dichroism Spectroscopy of a Recombinant Human Lactoferrin

“…The production of recombinant proteins in eukaryotic systems is well documented, specifically using yeasts such as Pichia pastoris , now renamed Komagataella phaffi ; the yeast species Pichia was transferred to the monotypic genus Komagataella and was represented by two species, K. pastoris and K. phaffi [ 15 ]. In this yeast, high levels of expression of proteins such as human lactoferrin have been reported with different expression vectors, such as pPIC9K, among others [ 16 , 17 ]. Obtaining high yields of a recombinant protein has always been the most important challenge.…”