GENOMICALLY RECODED ORGANISMS (GROS): REWRITING LIFE’S CODE FOR NOVEL APPLICATIONS IN PROTEIN-BASED BIOMATERIALS ENGINEERING

Abstract

Genomically recoded organisms (GROs) represent a major advancement in synthetic biology, enabling the deliberate redesign of the genetic code to expand the functional capabilities of living systems. By combining genome-wide codon reassignment with orthogonal translation systems, GROs facilitates the incorporation of noncanonical amino acids (ncAAs) into proteins, thereby extending the chemical diversity beyond that provided by the twenty canonical amino acids. These technologies allow precise modification of translational machinery, enabling the synthesis of proteins with novel structural, catalytic, and physicochemical properties. Recent advances in genome engineering platforms, including multiplex automated genome engineering, conjugative assembly genome engineering, and CRISPR-based technologies, have accelerated the development of GROs with enhanced translational flexibility, viral resistance, and intrinsic biocontainment features. The ability to incorporate ncAAs has expanded applications in protein engineering through site-specific functionalization, multisite amino acid incorporation, and the development of proteins with improved stability and catalytic performance. Furthermore, GRO-derived proteins have emerged as promising building blocks for advanced biomaterials, including self-assembling protein polymers, functional hydrogels, bioorthogonally cross-linked materials, and stimuli-responsive systems. Despite these advances, challenges related to cellular fitness, translational efficiency, metabolic burden, evolutionary stability, and industrial scalability remain significant barriers to broader implementation. This review summarizes recent progress in GRO engineering, orthogonal translation technologies, and genetic code expansion, with particular emphasis on their applications in advanced protein engineering and biomaterial design. Additionally, the biosafety implications, current limitations, and future prospects of GRO-based technologies are discussed.