Synthetic communities of Yarrowia lipolytica for efficient betanin bioproduction through metabolic partitioning

In bioproduction, synthetic microbial consortia have the potential to outcompete single-strain systems by distributing metabolic burden and partitioning tasks more effectively. Obligatory cross-feeding of essential metabolites, or syntrophy, is a promising strategy to stabilize consortium composition and prevent population drift. In this study, we screened 56 co-auxotrophic pairs capable of establishing syntrophy in the unconventional yeast Yarrowia lipolytica. Further characterization of these consortia revealed diverse growth dynamics and population distributions across various inoculation ratios. A selection of syntrophic consortia was evaluated for the production of the natural value-added pigment, betanin, as a proof-of-concept. By redistributing the metabolic load across different co-culture designs, we achieved higher betanin titers (136.2 mg/L) in syntrophic co-cultures compared to monoculture by 1.5-fold in microbioreactor conditions. This study provides a platform of Y. lipolytica syntrophic consortia to produce metabolically demanding compounds more efficiently.