Adaptive laboratory evolution of microbial co‐cultures for improved metabolite secretion |
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Authors: | Dimitrios Konstantinidis Filipa Pereira EvaMaria Geissen Kristina Grkovska Eleni Kafkia Paula Jouhten Yongkyu Kim Saravanan Devendran Michael Zimmermann Kiran Raosaheb Patil |
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Institution: | 1. Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg Germany ; 2. Faculty of Biosciences, Heidelberg University, Heidelberg Germany ; 3. Medical Research Council Toxicology Unit, Cambridge UK ; 4. VTT Technical Research Centre of Finland Ltd, Espoo Finland ;5.Present address: Life Science Institute, University of Michigan, Ann Arbor USA ;6.Present address: Brain Research Institute, Korea Institute of Research and Technology, Seoul South Korea |
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Abstract: | Adaptive laboratory evolution has proven highly effective for obtaining microorganisms with enhanced capabilities. Yet, this method is inherently restricted to the traits that are positively linked to cell fitness, such as nutrient utilization. Here, we introduce coevolution of obligatory mutualistic communities for improving secretion of fitness‐costly metabolites through natural selection. In this strategy, metabolic cross‐feeding connects secretion of the target metabolite, despite its cost to the secretor, to the survival and proliferation of the entire community. We thus co‐evolved wild‐type lactic acid bacteria and engineered auxotrophic Saccharomyces cerevisiae in a synthetic growth medium leading to bacterial isolates with enhanced secretion of two B‐group vitamins, viz., riboflavin and folate. The increased production was specific to the targeted vitamin, and evident also in milk, a more complex nutrient environment that naturally contains vitamins. Genomic, proteomic and metabolomic analyses of the evolved lactic acid bacteria, in combination with flux balance analysis, showed altered metabolic regulation towards increased supply of the vitamin precursors. Together, our findings demonstrate how microbial metabolism adapts to mutualistic lifestyle through enhanced metabolite exchange. |
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Keywords: | coevolution experimental evolution metabolic cooperation multi‐ omics vitamin secretion |
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