Abstract
Fuels and polymer precursors are widely used in daily life and in many industrial processes. Although these compounds are mainly derived from petrol, bacteria and yeast can produce them in an environment-friendly way. However, these molecules exhibit toxic solvent properties and reduce cell viability of the microbial producer which inevitably impedes high product titers. Hence, studying how product accumulation affects microbes and understanding how microbial adaptive responses counteract these harmful defects helps to maximize yields. Here, we specifically focus on the mode of toxicity of industry-relevant alcohols, terpenoids and aromatics and the associated stress-response mechanisms, encountered in several relevant bacterial and yeast producers. In practice, integrating heterologous defense mechanisms, overexpressing native stress responses or triggering multiple protection pathways by modifying the transcription machinery or small RNAs (sRNAs) are suitable strategies to improve solvent tolerance. Therefore, tolerance engineering, in combination with metabolic pathway optimization, shows high potential in developing superior microbial producers.
Highlights
Biosynthetic pathways of various microorganisms have been exploited and optimized to produce valuable biochemicals and fuel molecules with solvent properties [1,2].Recent concerns about crude oil availability and climate change further encourages the use of microbes in synthesizing solvent chemicals [3]
While the previous challenges are largely dependent on the process parameters, end-product toxicity is inherently linked to the production of fuels and biochemicals and becomes more dominant towards the end of the fermentation cycle [9]
These solvent molecules differ in terms of chemical properties, this review focuses on the common
Summary
Biosynthetic pathways of various microorganisms have been exploited and optimized to produce valuable biochemicals and fuel molecules with solvent properties [1,2]. Researchers started to focus on non-model producers (e.g., Corynebacterium glutamicum) and less conventional chemicals (e.g., styrene) which resulted in more industry-relevant strains by manipulating stress-response pathways [14,15] These examples illustrate that microbial tolerance engineering, along with metabolic engineering, is relevant in reaching economically attractive titers of alcohols, aromatics and more complex terpenoids in a variety of microbial species (Table 1). C. acetobutylicum and beijerinckii have the natural ability to metabolize sugars into acetone, butanol and ethanol simultaneously These strains have been used for over 100 years to produce this solvent mix on an industrial scale. As they need to withstand ethanol percentages (>10%), lactic acid bacteria are suitable candidates to study alcohol tolerance This yeast species is without any doubt the most commonly used fermentation strain both in the food and fuel industries. This feature is interesting in lignocellulose-based bioethanol production settings
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