Strategies to increase tolerance and robustness of industrial microorganisms

Abstract

The development of a cost-competitive bioprocess requires that the cell factory converts the feedstock into the product of interest at high rates and yields. However, microbial cell factories are exposed to a variety of different stresses during the fermentation process. These stresses can be derived from feedstocks, metabolism, or industrial production processes, limiting production capacity and diminishing competitiveness. Improving stress tolerance and robustness allows for more efficient production and ultimately makes a process more economically viable. This review summarises general trends and updates the most recent developments in technologies to improve the stress tolerance of microorganisms. We first look at evolutionary, systems biology and computational methods as examples of non-rational approaches. Then we review the (semi-)rational approaches of membrane and transcription factor engineering for improving tolerance phenotypes. We further discuss challenges and perspectives associated with these different approaches.

Exploring Yeast Diversity to Produce Lipid-Based Biofuels from Agro-Forestry and Industrial Organic Residues

“…The unveiling of the molecular mechanisms and functional pathways involved in yeast cell response to toxicants is essential to guide the genetic manipulation of oleaginous yeasts to improve tolerance. The use of lignocellulosic and industrial organic residues biomass for the production of added-value chemicals is a challenging task since yeast cells need to cope with multiple bioprocess-related stresses, either individually or combined, emphasising the relevance of enhancing multiple stress tolerance to maximise their performance in industrial production [ 89 , 261 , 262 , 263 , 264 ]. Physical and chemical extracellular stresses include non-optimum ranges of temperature and pH, osmotic pressure and the presence of growth inhibitors [ 89 , 261 , 262 , 263 , 264 ].…”

“…The use of lignocellulosic and industrial organic residues biomass for the production of added-value chemicals is a challenging task since yeast cells need to cope with multiple bioprocess-related stresses, either individually or combined, emphasising the relevance of enhancing multiple stress tolerance to maximise their performance in industrial production [ 89 , 261 , 262 , 263 , 264 ]. Physical and chemical extracellular stresses include non-optimum ranges of temperature and pH, osmotic pressure and the presence of growth inhibitors [ 89 , 261 , 262 , 263 , 264 ]. Despite being considered synonyms in some contexts, the concepts of tolerance and robustness may not coincide.…”

“…It is known that growth inhibitors present in lignocellulosic hydrolysates may compromise the integrity, fluidity and selective permeability of yeast plasma membrane [ 269 ]. For this reason, the majority of membrane engineering attempts to increase tolerance to multiple stresses target the modulation of its lipid composition, in order to maintain the integrity and fluidity under stress, namely by altering lipid saturation or changing the length of lipid in biomembranes [ 264 ]. The genetic manipulation of oleaginous yeasts, comprising the degree of saturation of lipids [ 200 , 223 , 243 , 244 , 270 , 271 , 272 ] or the length of the lipidic chain [ 273 , 274 ] led to increased lipid titers.…”

Pathway and protein engineering for biosynthesis

“…Synthetic biology tools and advanced technologies can accelerate the engineering of the pathways and enzymes in a high throughput manner. Two review articles included in this special issue summarized the recent progresses on technological developments to improve the stress tolerance of microorganisms [ 12 ] and engineering of pathways and genomes [ 13 ], respectively. Base editing technology has opened a new avenue for genome engineering, however it still suffers from limited availability of editable sites in the target bacterial genome.…”

Transcriptome profiles of high-lysine adaptation reveal insights into osmotic stress response in Corynebacterium glutamicum

“…In past decades, engineering the robustness of strains to industrially relevant stress factors has proven to be conducive to achieving higher yield and productivity ( Mukhopadhyay, 2015 ; Ko et al, 2020 ; Liu et al, 2021 ; Mohedano et al, 2022 ). However, the underlying mechanisms of how C. glutamicum tolerates high-lysine concentrations are still unclear, which obviously impedes the identification of promising targets for improving the robustness of cell factories.…”