Biological synthesis and anti-HeLa cells effect of glycosylated bafilomycins |
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| Affiliation: | 1. College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China;2. Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China;1. Department of Radiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China;2. Department of Stomatology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China;1. Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India;2. Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea;3. Department of Pharmaceutical Chemistry, Vinayaka Mission’s College of Pharmacy, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem 636308, Tamilnadu, India;4. Computational Drug Design Lab, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, India;5. Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Health Science Campus, Kochi-682 041, India;1. Department of Emergency, China-Japan Union Hospital of Jilin University, Changchun 130033, China;2. Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, China;1. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China;2. International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China;1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang, China;2. The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar, Heilongjiang, China |
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| Abstract: | Bafilomycin A1 (BAF A1) is a macrolide antibiotic that, in addition to its antibacterial activity, can induce apoptosis of cancer cells. Glycosylation plays an important role in the modification of antibiotics as it can improve their bioactivity. However, glycosylation of BAF A1 has not been previously reported. Bacillus licheniformis glycosyltransferase (GTs) Bl-YjiC and Bacillus subtilis GTs Bs-YjiC were expressed successfully in a heterologous manner. The glycosylation of BAF A1 with UDP-glucose, UDP-galactose or UDP-N-acetylglucosamine was catalyzed using the enzymes Bl-YjiC and Bs-YjiC. Our results demonstrated that Bl-YjiC can only utilize UDP-glucose as the donor, while Bs-YjiC can utilize all three glycosyl donors. The glycosylation site was demonstrated by MS/MS to be the hydroxyl group at the C21 position of BAF A1. The anti-proliferative effects of glucosyl BAF A1 (BAF-Glc) on HeLa cells indicate that this novel antibiotic is superior to BAF A1. The IC50 for BAF-Glc was determined to be 5.47 μM. Here, we report the production of glycosylated BAF A1 for the first time, and we show that the produced BAF-Glc exhibited better anticancer activity than BAF A1. This work provides theoretical and experimental support for the development of novel anticancer bafilomycins. |
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| Keywords: | Bafilomycin Glycosylation Anticancer Glycosyltransferase UDP-glucose |
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