Cell-PHactory: Exploiting phage as a source of novel synthetic biology tools to improve industrial fermentations.

As nature’s first bioengineers, bacteriophage have evolved to modify, adapt and control their bacterial hosts through billions of years of interactions. Indeed, like modern synthetic biologists aspire to do, bacteriophages already evade bacterial silencing of their xenogeneic DNA, subvert host gene expression, and co-opt both the central and peripheral host metabolisms of their hosts. Studying these key insights from a molecular systems biology perspective, inspired us to develop these evolutionary fully-adapted phage mechanisms as a next-level layer of synthetic biology tool.

As such, we tap into an unlimited source of novel phage tools (cargo) and genetic circuitry: (1) We exploit new phage-encoded genetic circuits as synthetic biology parts and as intricate biotechnological chassis.

(2) We build synthetic phage modulators (SPMs) as novel payloads to directly impact the bacterial metabolism in a targeted manner.

(3) We create designer bacteria by integrating SPMs-containing circuits into bacterial strains as proof-of-concepts for applications in industrial fermentations.

This proposed “plug-in” approach of evolutionary-adapted synthetic modules, will allow us to engineer Pseudomonas putida strains in new ways. By building proofs-of-concept for applications in industrial fermentations, this research offers potentially high-gain solutions for industry and biotechnology in general.