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.

糖肽抗生素是治疗由多重耐药的革兰氏阳性病原体引起的严重感染的最后手段。第一代糖肽（万古霉素和替考拉宁）是由土壤中的放线菌产生的。第二代糖肽（达巴万星，奥利万星和特拉万星）是祖先天然产物的半合成衍生物。在这里，我们涵盖了过去和现在的生物技术方法，以寻找和生产新旧糖肽类抗生素。我们回顾了增加微生物产量的策略（从经典菌株改良到合理的遗传工程），以及在基因组挖掘，化学酶衍生化，