Miles A Calzini, Alexandra A Malico, Melissa M Mitchler, Gavin J Williams
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Protein engineering for natural product biosynthesis and synthetic biology applications.
As protein engineering grows more salient, many strategies have emerged to alter protein structure and function, with the goal of redesigning and optimizing natural product biosynthesis. Computational tools, including machine learning and molecular dynamics simulations, have enabled the rational mutagenesis of key catalytic residues for enhanced or altered biocatalysis. Semi-rational, directed evolution and microenvironment engineering strategies have optimized catalysis for native substrates and increased enzyme promiscuity beyond the scope of traditional rational approaches. These advances are made possible using novel high-throughput screens, including designer protein-based biosensors with engineered ligand specificity. Herein, we detail the most recent of these advances, focusing on polyketides, non-ribosomal peptides and isoprenoids, including their native biosynthetic logic to provide clarity for future applications of these technologies for natural product synthetic biology.
期刊介绍:
Protein Engineering, Design and Selection (PEDS) publishes high-quality research papers and review articles relevant to the engineering, design and selection of proteins for use in biotechnology and therapy, and for understanding the fundamental link between protein sequence, structure, dynamics, function, and evolution.