TY - JOUR
T1 - Adaptive laboratory evolution of microbial co-cultures for improved metabolite secretion
AU - Konstantinidis, Dimitrios
AU - Pereira, Filipa
AU - Geissen, Eva Maria
AU - Grkovska, Kristina
AU - Kafkia, Eleni
AU - Jouhten, Paula
AU - Kim, Yongkyu
AU - Devendran, Saravanan
AU - Zimmermann, Michael
AU - Patil, Kiran Raosaheb
N1 - Funding Information:
We acknowledge the support of the following core facilities at the European Molecular Biology Laboratory (Heidelberg, Germany): Metabolomics (R. Gathungu), Genomics (V. Benes and R. Hercog), Proteomics (R. Mattel and F. Stein), Flow Cytometry (M. Paulsen and D. Ordonez) and Advanced Light Microscopy (S. Reither). We thank S. Blasche for providing the parental bacterial isolates used in this study. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement no. 866028).
Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2021/8/9
Y1 - 2021/8/9
N2 - 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.
AB - 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.
KW - coevolution
KW - experimental evolution
KW - metabolic cooperation
KW - multi-omics
KW - vitamin secretion
UR - http://www.scopus.com/inward/record.url?scp=85113790084&partnerID=8YFLogxK
U2 - 10.15252/msb.202010189
DO - 10.15252/msb.202010189
M3 - Article
C2 - 34370382
AN - SCOPUS:85113790084
SN - 1744-4292
VL - 17
JO - Molecular Systems Biology
JF - Molecular Systems Biology
IS - 8
M1 - e10189
ER -