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The economic upturn of the past 200 years would not have been conceivable without fossil resources such as coal and oil. However, the fossil-based economy increasingly reaches its limits and displays contradictions. Bioeconomy, strategically combining economy and ecology willing to make biobased and sustainable growth possible, is promising to make a significant contribution towards solving these issues. In this context, microbial bioconversions are promising to support partially the increasing need for materials and fuels starting from fresh, preferably waste, biomass. Butanol is a very attractive molecule finding applications both as a chemical platform and as a fuel. Today it principally derives from petroleum, but it also represents the final product of microbial catabolic pathways. Because of the need to maximize yield, titer and productivity to make the production competitive and viable, the challenge is to transform a robustly regulated metabolic network into the principal cellular activity. However, this goal can only be accomplished by a profound understanding of the cellular physiology, survival strategy and sensing/signalling cascades. Here, we shortly review on the natural cellular pathways and circumstances that lead to n-butanol accumulation, its physiological consequences that might not match industrial needs and on possible solutions for circumventing these natural constraints.

n-butanol: challenges and solutions for shifting natural metabolic pathways into a viable microbial production