Synthetic yeast-bacterium consortium enables co-inducible relayed synthesis of chemicals

Microbial coculture can integrate advantages and overcome the metabolic imbalance of individual species. Programming strain interactions represents a common routine for synthetic microbial communities with distinct species, which causes difficulties and redundant workloads in interaction construction before being available as chassis hosts. This study explores yeast-bacterium consortium without engineered interactions for the co-inducible relayed synthesis of natural products. The Komagataella phaffii-Escherichia coli consortium is explored for co-growth under selected conditions. Low-level glucose- and blue light-responsive transcriptional systems are rebuilt separately for each host, allowing single-signal co-induced activation of compound synthesis in coculture. Pathway redirection, genome mining, and rewiring of key targets for acyl donor degradation result in efficient production of the reporter molecule simvastatin (26.2 mg l^-1) through living consortium cultured on simple carbon source. Inducible biosynthesis of another reporter compound (2S)-naringenin (165.6 mg l^-1) further validates the extendibility of this community. The described platform represents a breakthrough in engineering microbial consortium for biosynthesis.