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Decoding and engineering tetracycline biosynthesis
Authors:Lauren B. Pickens  Yi Tang
Affiliation:1. Departamento de Química, CICECO, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;2. Departamento de Tecnologia Bioquímico-Farmacêutica, Universidade de São Paulo, Avenida Prof. Lineu Prestes 580, Bl. 16, 05508-900 São Paulo, SP, Brazil;3. Universidade Federal de Pernambuco, Centro de Ciências Biológicas, Departamento de Antibióticos. Rua Prof. Artur de Sá, Cidade Universitária, 50670-420 Recife, PE, Brazil;1. The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK;2. Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada 2501 Sur, Monterrey, NL 64849, Mexico;3. Department of Bioprocess and Biotechnology, School of Pharmaceutical Sciencies, Universidade Estadual Paulista, Rodovia Araraquara-Jau Km. 01, CEP 14801-902, Araraquara, SP, Brazil;4. CICECO – Aveiro Institute of Materials, Chemistry Department, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;5. Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Av. Morones Prieto 3000 Pte, Col. Los Doctores, Monterrey, NL 64710, Mexico;1. Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstrasse 7, 38124, Braunschweig, Germany;2. German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124, Braunschweig, Germany;3. Department of Drug Design and Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany;4. Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany;5. Department of Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstrasse 7, 38124, Braunschweig, Germany;1. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States;2. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, United States;3. Engineering Research Center of Industrial Microbiology (Ministry of Education), College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350108, China;4. State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200030, China;1. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States;2. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, United States
Abstract:Tetracyclines have been important agents in combating infectious disease since their discovery in the mid-20th century. Following widespread use, tetracycline resistance mechanisms emerged and continue to create a need for new derivatives that are active against resistant bacterial strains. Semisynthesis has led to second and third generation tetracycline derivatives with enhanced antibiotic activity and pharmacological properties. Recent advancement in understanding of the tetracycline biosynthetic pathway may open the door to broaden the range of tetracycline derivatives and afford analogs that are difficult to access by synthetic chemistry.
Keywords:
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