Regueira López, AlberteLema Rodicio, Juan ManuelMauricio Iglesias, Miguel2021-02-182022-02-022021Current Opinion in Biotechnology Volume 67, February 2021, Pages 130-1400958-1669http://hdl.handle.net/10347/24496Microorganisms extract energy from substrates following strategies that may seem suboptimal at first glance. Beyond the so-called yield-rate trade-off, resource allocation models, which focus on assigning different functional roles to the limited number of enzymes that a cell can support, offer a framework to interpret the inefficient substrate use by microorganisms. We review here relevant examples of substrate conversions where a significant part of the available energy is not utilised and how resource allocation models offer a mechanistic interpretation thereof, notably for open mixed cultures. Future developments are identified, in particular, the challenge of considering metabolic flexibility towards uncertain environmental changes instead of strict fixed optimality objectives, with the final goal of increasing the prediction capabilities of resource allocation models. Finally, we highlight the relevance of resource allocation to understand and enable a promising biorefinery platform revolving around lactate, which would increase the flexibility of waste-to-chemical biorefinery schemeseng© 2021 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article10.1016/j.copbio.2021.01.015open access