Nature's Nanotech Warriors: The Role of Metalloproteins and Protein Cages for Environmental Remediation

ABSTRACT Heavy metal toxicity threatens human health and environmental sustainability. Rising pollution stems directly from expanding mining and industrial activities, contaminating air, water, and soil. Conventional remediation relies on costly physical extraction and chemical precipitation, which require extensive infrastructure. Bioremediation using biological systems offers a sustainable, eco‐friendly, and efficient alternative. This review highlights protein‐based systems designed for effective bioremediation. In nature, metalloproteins like metallothioneins, phytochelatins, P ‐type ATPases, phosphatases, and self‐assembling cages such as ferritins evolved mainly by bacteria over millions of years to remove heavy metals. These proteins sequester metals via high‐affinity binding sites, while ferritin cages encapsulate them through electrostatic interactions and oxidation. Metal sequestration mechanisms are explored and studied, optimizing these via protein engineering, synthetic biology, and AI techniques for efficient biomaterials. Over the last two decades, protein systems have been used for cadmium, lead, mercury, arsenic, and uranium biomineralization. Despite successes, challenges like reusability, scalability, and cost persist. Recent advances in protein engineering and AI have yielded selective, scalable protein cage designs with engineered metal‐binding sites, inspired by metalloproteins. This interdisciplinary field promises effective solutions to heavy metal pollution, gaining momentum and attracting multidisciplinary researchers for an exciting future.