A Modular PLUG-IN Photosynthetic Chassis With Tunable Thermal Control for Mammalian Systems

Microalgae are promising photosynthetic platforms for high-value compounds, yet their industrial use is often hindered by a trade-off between robust growth and the metabolic burden of payload production or cell wall disruption. Constitutive engineering for these traits compromises cultivator fitness. Here we report the development of a versatile, thermal-regulated "PLUG-IN" chassis in Nannochloropsis oceanica that enables programmable control of metabolic output and cell integrity. Comparative transcriptomics identify two highly heat-inducible promoters (P_NoED and P_NoUK), which we use to construct a modular thermal gene-amplification. Heat-activated AtWRI1 expression enhances triacylglycerol and eicosapentaenoic acid accumulation, while temperature-dependent silencing of the cellulose synthase gene CesA1 triggers rapid cell-wall weakening without affecting growth under permissive conditions. Coupling metabolic and cell-wall modules yields strains capable of grind-free lipid recovery and substantially improved intracellular product accessibility. Notably, these engineered thermally controlled programs remain functional in mammalian hosts, demonstrating cross-kingdom compatibility. This work establishes a "plug-in" chassis compatible with mammalian systems that synchronizes growth, production, and cell-wall re-configuration, providing a versatile platform for photosynthetic bioproduction and microalgal synthetic biology.