Genetic Programming of Bacterial Microcompartments: Operon Order as a Tool for Nanoscale Morphogenesis

Abstract Gene order is a powerful design principle for protein nanomachines. In nature, gene organisation ensures the precise assembly of functional protein nanostructures. We demonstrate how 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 compartmentalised 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 customised geometries and activities. Competing Interest Statement The authors have declared no competing interest.