Biochemical Programming of the Fungal Cell Wall: A Synthetic Biology Blueprint for Advanced Mycelium-Based Materials

The global drive toward a circular bioeconomy is accelerating the demand for sustainable, high-performance materials. Filamentous fungi offer a compelling solution, functioning as living foundries that transform low-value biomass into advanced materials via self-assembly. Mycelium-based composites have proven potential, yet progress has been dominated by empirical screening of fungal species and substrates. Realizing their full capabilities requires a paradigm shift toward rational design. This review introduces a conceptual framework centered on the biochemical programming of the fungal cell wall. Viewed through a materials science lens, the cell wall is a dynamic, hierarchical nanocomposite whose properties can be deliberately tuned. We analyze the contributions of its principal components—the chitin-glucan structural scaffold, the glycoprotein functional matrix, and surface-active hydrophobins—to the bulk characteristics of mycelium-derived materials. We then identify biochemical levers for controlling these properties. External factors such as substrate composition and environmental cues (e.g., pH) modulate cell wall architecture through conserved signaling pathways. Complementing these, an internal synthetic biology toolkit enables direct genetic and chemical intervention. Strategies include targeted engineering of biosynthetic and regulatory genes (e.g., CHS, AGS, GCN5), chemical genetics to dynamically adjust synthesis during growth, and modification of surface chemistry for specialized applications like tissue engineering. By integrating fungal cell wall biochemistry, materials science, and synthetic biology, this framework moves the field from incidental discovery toward the intentional creation of smart, functional, and sustainable mycelium-based materials—aligning material innovation with the imperatives of the circular bioeconomy.