SCULPT-MCP: Systematic Chromosomal Upgrades for Locus-Driven Protein Topologies in Microcompartments

Abstract Gene order is a powerful design principle for protein nanomachines. In nature, gene organization ensures the precise assembly of functional protein nanostructures. We demonstrate how the genetic repositioning of the key structural gene pduN within the operon encoding a self-assembling protein nanocompartment sculpts the morphology and function of bacterial microcompartments (BMCs). Relocating pduN to new operonic positions dramatically altered the size, shape, and catalytic output of BMCs, despite identical protein sequences. These shifts reveal how gene order may control nanoscale assembly and compartmentalized function. Our findings establish operon architecture as a programmable genetic framework for nanostructure morphogenesis and provide a synthetic biology strategy to engineer self-assembling nanodevices with customized geometries and activities.