The Plasma Membrane at the Cornerstone Between Flexibility and Adaptability: Implications for Saccharomyces cerevisiae as a Cell Factory.

Luís Ferraz,Maria João Sousa,Paola Branduardi,Michael Sauer

doi:10.3389/fmicb.2021.715891

Abstract

In the last decade, microbial-based biotechnological processes are paving the way toward sustainability as they implemented the use of renewable feedstocks. Nonetheless, the viability and competitiveness of these processes are often limited due to harsh conditions such as: the presence of feedstock-derived inhibitors including weak acids, non-uniform nature of the substrates, osmotic pressure, high temperature, extreme pH. These factors are detrimental for microbial cell factories as a whole, but more specifically the impact on the cell’s membrane is often overlooked. The plasma membrane is a complex system involved in major biological processes, including establishing and maintaining transmembrane gradients, controlling uptake and secretion, intercellular and intracellular communication, cell to cell recognition and cell’s physical protection. Therefore, when designing strategies for the development of versatile, robust and efficient cell factories ready to tackle the harshness of industrial processes while delivering high values of yield, titer and productivity, the plasma membrane has to be considered. Plasma membrane composition comprises diverse macromolecules and it is not constant, as cells adapt it according to the surrounding environment. Remarkably, membrane-specific traits are emerging properties of the system and therefore it is not trivial to predict which membrane composition is advantageous under certain conditions. This review includes an overview of membrane engineering strategies applied to Saccharomyces cerevisiae to enhance its fitness under industrially relevant conditions as well as strategies to increase microbial production of the metabolites of interest.

Highlights

The urge for the production of goods and services for a growing population, adopting the principles of linear economy, has led to massive consumption of natural resources, resulting in an unbalance between the request and the supply of these resources
This review aims to describe the most recent efforts to engineer the plasma membrane of microbial cell factories, with particular emphasis on S. cerevisiae, to increase its fitness and performance in biotechnological processes
Identification and quantification of lipids Physiochemical characterization of the plasma membrane Working on living cells under physiological relevant conditions, Investigation of cell surface nanomechanical properties Enables the prediction of physiochemical properties of lipid bilayers Helpful to predict phenotypes based on genotype manipulation

Summary

INTRODUCTION

The urge for the production of goods and services for a growing population, adopting the principles of linear economy, has led to massive consumption of natural resources, resulting in an unbalance between the request and the supply of these resources. The plasma membrane has to be considered when designing strategies for the development of versatile, robust and efficient cell factories ready to tackle the harshness of industrial processes while delivering high yield, titer and productivity In this sense, the concept of membrane engineering has emerged. The biosynthesis pathways leading to different lipid species are tightly connected with complex cross-talks (Henry et al, 2012) Another major component of the plasma membrane is proteins, representing around 40% of the membrane composition. The correct positioning and activity of Pma into plasma membrane lipid rafts has been correlated with the presence of very long chain fatty acids and ergosterol (Eisenkolb et al, 2002; Gaigg et al, 2006) These studies highlighted the importance of membrane lipid composition for the correct integration and functioning of proteins in the plasma membrane. Identification and quantification of lipids Physiochemical characterization of the plasma membrane Working on living cells under physiological relevant conditions, Investigation of cell surface nanomechanical properties Enables the prediction of physiochemical properties of lipid bilayers Helpful to predict phenotypes based on genotype manipulation

Limitations

Findings

CONCLUSION