Engineering Plant\nMetabolism for Synthesizing Amino\nAcid Derivatives of Animal Origin Using a Synthetic Modular Approach

The biosynthesis of amino acid derivatives of animal\norigin in\nplants represents a promising frontier in synthetic biology, offering\na sustainable and eco-friendly approach to enhancing the nutritional\nvalue of plant-based diets. This study leverages the versatile capabilities\nof Nicotiana benthamiana as a transient\nexpression system to test a synthetic modular framework for the production\nof creatine, carnosine, and taurine-compounds typically absent in\nplants but essential for human health. By designing and stacking specialized\nsynthetic modules, we successfully redirected the plant metabolic\nflux toward the synthesis of these amino acid derivatives of animal\norigin. Our results revealed the expression of a standalone creatine\nmodule resulted in the production of 2.3 μg/g fresh weight of\ncreatine in N. benthamiana leaves.\nIntegrating two modules significantly carnosine yield increased by\n3.8-fold and minimized the impact on plant amino acid metabolism compared\nto individual module application. Unexpectedly, introducing the taurine\nmodule caused a feedback-like inhibition of plant cysteine biosynthesis,\nrevealing complex metabolic adjustments that can occur when introducing\nforeign pathways. Our findings underline the potential for employing\nplants as biofactories for the sustainable production of essential\nnutrients of animal origin.