(188at) Enhancing Phenol Biosynthesis By Exploiting Modular Co-Culture Engineering Strategies

Microbial bioproduction of aromatic compound phenol is of great research interest, as it offers a renewable method for replacing existing petroleum-based phenol production. In this study, we adapted modular co-culture engineering strategy to construct two E. coli-E. coli co-culture systems for phenol over-production. In the first co-culture, the biosynthetic pathway leading from glucose to 4-hydroxybenzoate and then phenol was divided into two modules, each of which was harbored by one metabolically engineered E. coli strain, respectively. Similarly in the second co-culture, two E. coli strains were engineered to accommodate the biosynthetic pathway leading from glucose to phenol via tyrosine. The optimization of the co-culture biosynthesis, including enhancing pathway intermediate provision, balancing the upstream and downstream pathway modules’ bioconversion capabilities, and varying the cultivation conditions, led to an appreciable level of phenol production. Importantly, it was shown that the phenol bioproduction by the constructed co-cultures were significantly higher than the production by the corresponding E. coli mono-cultures, indicating the strong potential of modular co-culture engineering for improving the performance of microbial biosynthesis.