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

ABSTRACT 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.