Caice Liang, Jing Ruan, Biao Yang, Wei Liu, Qingguo Liu, Chaowei Zhou, Junqiang Shan, Shuqi Shi, Hui Han, Wenjun Sun, Yong Chen
Biofilm-based manufacturing offers superior robustness, yet the spatial logic governing its metabolic resilience remains a "black box," hindering rational strain engineering. Here, we present a spatiotemporal transcriptomic map of Saccharomyces cerevisiae biofilms under industrial conditions. We identify a fundamental "reproduction-metabolism decoupling" strategy: the biofilm functions as a self-organizing system where outer cells act as a "metabolic shield"-activating retrograde signaling to endure stress and maximize glycolysis-while inner cells serve as a "protected nursery" for rapid proliferation. This spatial division of labor explains biofilm stability and provides a genetic blueprint for spatially programming microbial factories for next-generation biomanufacturing.