A Wake-Up Call for the Efficient Use of the Bacterial Resting Cell Process, with Focus on Low Solubility Products

Micro-organisms are often subjected to stressful conditions. Owing to their capacity to adapt, they try to rapidly cope with the unfavorable conditions by lowering their growth rate, changing their morphology, and developing altered metabolite production and other stress-related metabolism. The stress-related metabolism of the cells which interrupted their growth is often referred to as resting metabolism and can be exploit for specific and high rate production of secondary metabolites. Although the bacterial resting cell process has been described decades ago, we find it worthwhile to bring the process under renewed attention and refer to this type of processes as non-growing metabolically active (NGMA) cell processes. Despite their use may sound counterproductive, NGMA cells can be of interest to increase substrate conversion rates or enable conversion of certain substrates, not accessible to growing cells due to their bacteriostatic nature or requirement of resistance to a multitude of different stress mechanisms. Biomass reuse is an interesting feature to improve the economics of NGMA cell processes. Yet, for lipophilic compounds or compounds with low solubility, biomass separation can be delicate. This review draws the attention on existing examples of NGMA cell processes, summarizing some developmental tools and highlighting drawbacks and opportunities, to answer the research question if NGMA cells can have a distinct added value in industry. Particular elaboration is made on a novel and more broadly applicable strategy to enable biomass reuse for conversions of compounds with low solubility.