Structure-driven protein engineering for production of valuable natural products. (April 2023)

• Record Type: Journal Article
• Authors: Wang, Yun; Yu, Luyao; Shao, Jie; Zhu, Zhanpin; Zhang, Lei
• Is Part Of: Trends in plant science. Volume 28:Number 4(2023)
• Page Start: 460
• Page End: 470
• Publication Date: 2023-04
• Subjects: protein structure -- rational design -- modification -- synthetic biology -- chemoenzymatic synthesis -- plant metabolic engineering; Botany -- Periodicals; Botanique -- Périodiques; Botany; Periodicals; 580.5
• DOI: 10.1016/j.tplants.2022.11.004
• Languages: English
• ISSNs: 1360-1385

Abstract

Abstract: Proteins are the most frequently used biocatalysts, and their structures determine their functions. Modifying the functions of proteins on the basis of their structures lies at the heart of protein engineering, opening a new horizon for metabolic engineering by efficiently generating stable enzymes. Many attempts at classical metabolic engineering have focused on improving specific metabolic fluxes and producing more valuable natural products by increasing gene expression levels and enzyme concentrations. However, most naturally occurring enzymes show limitations, and such limitations have hindered practical applications. Here we review recent advances in protein engineering in synthetic biology, chemoenzymatic synthesis, and plant metabolic engineering and describe opportunities for designing and constructing novel enzymes or proteins with desirable properties to obtain more active natural products. Highlights: The principle of structure-driven protein engineering is to derive key residues for enzyme function and explain the catalytic principles of enzymes on the basis of authentic structural analysis. Structure-driven protein engineering has become an effective method for improving the directed evolution of functional enzymes. Advances in synthetic biology techniques, such as high-precision genome editing and high-throughput screening, would in turn facilitate protein engineering and accelerate the process of obtaining the desired protein. Metabolic engineering rationalizes the design of elite structure-oriented genes to improve endogenous metabolic networks in plants. Structure-based protein engineering combined with the chemoenzymatic approach has provided new insights into the synthesis of complex natural products.