Department of Biotechnology, Crystal Pharma, A Subsidiary of Albany Molecular Research Inc. (AMRI), Parque Tecnológico de León, León, Spain.
Methods Mol Biol. 2021;2296:351-363. doi: 10.1007/978-1-0716-1358-0_20.
Daptomycin is a cyclic lipopeptide antibiotic with potent activity against gram-positive bacteria. It has a calcium-dependent mechanism of action that disrupts multiple features of the bacterial membrane function. This antibiotic is highly demanded due to its effectiveness against to microorganisms resistant to other antibiotics, including vancomycin-resistant Staphylococcus aureus (VRSA) and methicillin-resistant S. aureus (MRSA). Daptomycin is produced by fermentation of Streptomyces roseosporus, currently identified as Streptomyces filamentosus. However, low fermentation yields and high production costs are reported. This chapter describes a method of strain improvement involving random mutagenesis, rational screening by bioassay, and flask fermentation. The ultimate objective is to select mutants of S. roseosporus overproducing daptomycin in order to design a more cost-effective daptomycin production.
达托霉素是一种具有抗革兰氏阳性菌活性的环状脂肽抗生素。它具有依赖于钙的作用机制，可破坏细菌膜功能的多种特征。由于其对其他抗生素（包括耐万古霉素金黄色葡萄球菌（VRSA）和耐甲氧西林金黄色葡萄球菌（MRSA））具有有效性，因此该抗生素需求量很大。达托霉素通过玫瑰孢链霉菌的发酵产生，目前被鉴定为丝状链霉菌。然而，据报道，其发酵产率低且生产成本高。本章介绍了一种涉及随机诱变、生物测定的合理筛选和摇瓶发酵的菌株改良方法。最终目标是选择产生达托霉素过量的玫瑰孢链霉菌突变体，以设计更具成本效益的达托霉素生产。
