Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy; The Protein Factory Research Center, Politecnico di Milano and University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
Biotechnol Adv. 2018 Mar-Apr;36(2):534-554. doi: 10.1016/j.biotechadv.2018.02.009. Epub 2018 Feb 15.
Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by multi-drug resistant Gram-positive pathogens. First-generation glycopeptides (vancomycin and teicoplanin) are produced by soil-dwelling actinomycetes. Second-generation glycopeptides (dalbavancin, oritavancin, and telavancin) are semi-synthetic derivatives of the progenitor natural products. Herein, we cover past and present biotechnological approaches for searching for and producing old and new glycopeptide antibiotics. We review the strategies adopted to increase microbial production (from classical strain improvement to rational genetic engineering), and the recent progress in genome mining, chemoenzymatic derivatization, and combinatorial biosynthesis for expanding glycopeptide chemical diversity and tackling the never-ceasing evolution of antibiotic resistance.
糖肽类抗生素是治疗由耐多药革兰阳性病原体引起的严重感染的最后手段。第一代糖肽类药物（万古霉素和替考拉宁）由土壤放线菌产生。第二代糖肽类药物（达巴万星、奥他万星和替拉万星）是前体天然产物的半合成衍生物。本文综述了过去和现在用于寻找和生产新旧糖肽类抗生素的生物技术方法。我们回顾了增加微生物产量的策略（从经典的菌株改良到合理的基因工程），以及基因组挖掘、化学酶衍生化和组合生物合成在扩大糖肽化学多样性和解决抗生素耐药性不断进化方面的最新进展。
