Roberto Mazzoli

In the last decades, fermentative production of n‐butanol has regained substantial interest mainly owing to its use as drop‐in‐fuel. The use of lignocellulose as an alternative to traditional acetone–butanol–ethanol fermentation feedstocks (starchy biomass and molasses) can significantly increase the economic competitiveness of biobutanol over production from non‐renewable sources (petroleum). However, the low cost of lignocellulose is offset by its high recalcitrance to biodegradation which generally requires chemical‐physical pre‐treatment and multiple bioreactor‐based processes. The development of consolidated processing (i.e., single‐pot fermentation) can dramatically reduce lignocellulose fermentation costs and promote its industrial application. Here, strategies for developing microbial strains and consortia that feature both efficient (hemi)cellulose depolymerization and butanol production will be depicted, that is, rational metabolic engineering of native (hemi)cellulolytic or native butanol‐producing or other suitable microorganisms; protoplast fusion of (hemi)cellulolytic and butanol‐producing strains; and co‐culture of (hemi)cellulolytic and butanol‐producing microbes. Irrespective of the fermentation feedstock, biobutanol production is inherently limited by the severe toxicity of this solvent that challenges process economic viability. Hence, an overview of strategies for developing butanol hypertolerant strains will be provided.