TY - JOUR

T1 - Folding of heterologous proteins in bacterial cell factories

T2 - Cellular mechanisms and engineering strategies

AU - Rong, Yixin

AU - Jensen, Sheila Ingemann

AU - Lindorff-Larsen, Kresten

AU - Nielsen, Alex Toftgaard

N1 - Publisher Copyright: © 2022

PY - 2023

Y1 - 2023

N2 - The expression of correctly folded and functional heterologous proteins is important in many biotechnological production processes, whether it is enzymes, biopharmaceuticals or biosynthetic pathways for production of sustainable chemicals. For industrial applications, bacterial platform organisms, such as E. coli, are still broadly used due to the availability of tools and proven suitability at industrial scale. However, expression of heterologous proteins in these organisms can result in protein aggregation and low amounts of functional protein. This review provides an overview of the cellular mechanisms that can influence protein folding and expression, such as co-translational folding and assembly, chaperone binding, as well as protein quality control, across different model organisms. The knowledge of these mechanisms is then linked to different experimental methods that have been applied in order to improve functional heterologous protein folding, such as codon optimization, fusion tagging, chaperone co-production, as well as strain and protein engineering strategies.

AB - The expression of correctly folded and functional heterologous proteins is important in many biotechnological production processes, whether it is enzymes, biopharmaceuticals or biosynthetic pathways for production of sustainable chemicals. For industrial applications, bacterial platform organisms, such as E. coli, are still broadly used due to the availability of tools and proven suitability at industrial scale. However, expression of heterologous proteins in these organisms can result in protein aggregation and low amounts of functional protein. This review provides an overview of the cellular mechanisms that can influence protein folding and expression, such as co-translational folding and assembly, chaperone binding, as well as protein quality control, across different model organisms. The knowledge of these mechanisms is then linked to different experimental methods that have been applied in order to improve functional heterologous protein folding, such as codon optimization, fusion tagging, chaperone co-production, as well as strain and protein engineering strategies.

KW - Bacterial

KW - Expression

KW - Folding

KW - Heterologous

KW - Host

KW - Platform

KW - Production

KW - Protein

U2 - 10.1016/j.biotechadv.2022.108079

DO - 10.1016/j.biotechadv.2022.108079

M3 - Review

C2 - 36528238

AN - SCOPUS:85144628378

VL - 63

JO - Biotechnology Advances

JF - Biotechnology Advances

SN - 0734-9750

M1 - 108079

ER -