Broad-Host-Range Synthetic Biology: Rethinking Microbial Chassis as a Design Variable
Dennis Tin Chat Chan, Johan Bjerg, Hans C. Bernstein
Abstract
Broad-host-range synthetic microbiology is redefining the role of microbial hosts in genetic design by moving beyond the traditional organisms. Historically, synthetic biology has focused on optimizing engineered genetic constructs within a limited set of well-characterized chassis, often treating host-context dependency as an obstacle. However, emerging research demonstrates that host selection is a crucial design parameter that influences the behavior of engineered genetic devices through resource allocation, metabolic interactions, and regulatory crosstalk. By leveraging microbial diversity, broad-host-range synthetic biology enhances the functional versatility of engineered biological systems, enabling a larger design space for biotechnology applications in biomanufacturing, environmental remediation, and therapeutics. The continued development of broad-host-range tools─including modular vectors and host-agnostic genetic devices─facilitates the expansion of chassis selection, improving system predictability and stability. This perspective highlights the advantages of incorporating host selection into synthetic biology design principles, positioning microbial chassis as tunable components rather than passive platforms.