Protein Engineering for Improving and Diversifying Natural Product Biosynthesis

In engineering the biosynthesis of natural products, protein engineering is paramount for modifying the characteristics of enzymes or genetically encoded biosensors. Protein engineering has improved the biosynthesis of natural products through enhancement of enzymatic activity, colocalization of enzyme complexes, improvement of protein stability, and engineering of sensor-regulators for better screening or dynamic regulation. Engineering existing proteins can yield variants with novel catalytic functions. These advances expand the spectrum of products and thus diversify the biosynthesis of natural products. Proteins found in nature have traditionally been the most frequently used biocatalysts to produce numerous natural products ranging from commodity chemicals to pharmaceuticals. Protein engineering has emerged as a powerful biotechnological toolbox in the development of metabolic engineering, particularly for the biosynthesis of natural products. Recently, protein engineering has become a favored method to improve enzymatic activity, increase enzyme stability, and expand product spectra in natural product biosynthesis. This review summarizes recent advances and typical strategies in protein engineering, highlighting the paramount role of protein engineering in improving and diversifying the biosynthesis of natural products. Future prospects and research directions are also discussed. Proteins found in nature have traditionally been the most frequently used biocatalysts to produce numerous natural products ranging from commodity chemicals to pharmaceuticals. Protein engineering has emerged as a powerful biotechnological toolbox in the development of metabolic engineering, particularly for the biosynthesis of natural products. Recently, protein engineering has become a favored method to improve enzymatic activity, increase enzyme stability, and expand product spectra in natural product biosynthesis. This review summarizes recent advances and typical strategies in protein engineering, highlighting the paramount role of protein engineering in improving and diversifying the biosynthesis of natural products. Future prospects and research directions are also discussed. proteins that can regulate transcription by binding to specific DNA sequences as well as to corresponding ligands to activate or repress downstream expression. aTF conformation changes take place during ligand binding. a method often used in protein engineering that mimics the process of natural selection to drive genes, RNAs, or proteins to evolve in a predefined direction. the ratio of the maximum signal to the minimum signal of a biosensor. This should be distinguished from the operational range – the concentration range of ligands over which the sensor shows changes in signal output. also called fusion proteins, these are generated by combining two or more separate proteins into a single or multiple polypeptide(s) that have functional properties derived from each of the original proteins. the ability of an enzyme to catalyze a side reaction in addition to its main function. Although enzymes are remarkably specific catalysts, they can often perform side reactions in addition to their main, native catalytic activity. a computational method for studying the physical interactions of atoms and molecules. In protein engineering, it usually refers to simulating the interaction between proteins and ligands. compounds that can be found in nature, especially secondary metabolites produced by plants, animals, or fungi. substitution of a key residue through separate mutation of the DNA sequence to encode each of the 20 natural amino acids.