Mitigating Winner-Take-All\nResource Competition through\nAntithetic Control Mechanism

Competition among genes for limited transcriptional and\ntranslational\nresources impairs the functionality and modularity of synthetic gene\ncircuits. Traditional control mechanisms, such as feedforward and\nnegative feedback loops, have been proposed to alleviate these challenges,\nbut they often focus on individual modules or inadvertently increase\nthe burden on the system. In this study, we introduce three novel\nmultimodule control strategieslocal regulation, global regulation,\nand negatively competitive regulation (NCR)that employ an\nantithetic regulatory mechanism to mitigate resource competition.\nOur systematic analysis reveals that while all three control mechanisms\ncan alleviate resource competition to some extent, the NCR controller\nconsistently outperforms both the global and local controllers. This\nsuperior performance stems from the unique architecture of the NCR\ncontroller, which is independent of specific parameter choices. Notably,\nthe NCR controller not only facilitates the activation of less active\nmodules through cross-activation mechanisms but also effectively utilizes\nthe resource consumption within the controller itself. These findings\nemphasize the critical role of carefully designing the topology of\nmultimodule controllers to ensure robust performance.