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Optimization of the production of the lantibiotic mutacin 1140 in minimal media
Institution:1. Mississippi State University, Department of Biological Sciences, Mississippi State, MS 39762, United States;2. Mississippi State University, Department of Entomology and Plant Pathology, Mississippi State, MS 39762, United States;3. Department of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany;4. Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia;5. Department of Biological Chemistry, Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel;1. Department of Chemistry, Florida A&M University, Tallahassee, FL 32307, United States;2. Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32603, United States;3. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, United States;4. Feik School of Pharmacy, University of the Incarnate Word, San Antonio, TX 78209, United States;1. School of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China;2. Key Laboratory of Resources Chemistry of Nonferrous Metals, Central South University, Changsha 410083, China;1. Department of Chemical and Biochemical Engineering, University of Western Ontario, 1151 Richmond St., London, Ontario N6A 3K7, Canada;2. Sustainable Process Technology, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, Netherlands;3. Shell Global Solutions International, United States;4. RWTH Aachen, AVT – Biochemical Engineering, Worringerweg 1, 52074 Aachen, Germany;1. Laboratório Nacional de Energia e Geologia, Unidade de Bioenergia, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal;2. LEAF-Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal
Abstract:Mutacin 1140 is produced by Streptococcus mutans and belongs to the type A lantibiotic family. Experiments were done to optimize production of mutacin 1140 in minimal media enabling a more cost efficient downstream purification method. The development of a small volume fermentation method enabled a rapid screen of several variables in a standard shaking incubator. This method provided a fast approach for determining components that promote mutacin 1140 production in minimal media broth. Lactose was determined to be the optimal carbon source for mutacin 1140 production. High concentrations of CaCl2 (0.3%, w/v) and MgSO4 (0.77%, w/v) promoted an increase in mutacin 1140 production, while ZnCl2 and FeCl3 appeared to impair production. Optimization of mutacin 1140 production in minimal media resulted in more than a 100-fold increase in production compared to the base medium used to begin our optimizations. The yield has been estimated by RP-HPLC to be ∼10 mg/L.
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