Structure-driven protein engineering for production of valuable natural products |
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| Institution: | 1. Institute of Interdisciplinary Integrative Medicine Research, Medical School of Nantong University, Nantong 226001, China;2. Biomedical Innovation R&D Centre, School of Medicine, Shanghai University, Shanghai 200444, China;3. Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;4. Innovative Drug R&D Center, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China;1. International Genome Center, Jiangsu University, Zhenjiang 212013, China;2. State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of Ministry of Agriculture and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, China;1. Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu 610213, China;2. Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang 455000, China;3. Hainan Yazhou Bay Seed Laboratory, Sanya 572025, China;4. DynaMo Center, Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, Frederiksberg C 1871, Denmark;5. Max Planck Institute of Molecular Plant Physiology, Potsdam 14476, Germany;1. State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China;2. Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China;1. Guangdong Key Laboratory for Crop Germplasm Resources Preservation and Utilization, Agro-biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, Guangdong, China;2. Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany;1. Max-Planck-Institute of Molecular Plant Physiology, 14476 Potsdam-Golm, Germany;1. Shanghai Key Laboratory of Plant Molecular Sciences, College of Life Sciences, Shanghai Normal University, Shanghai 200234, China |
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| 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. |
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