Numerous important therapeutic agents, including widely-used antibiotics, anti-cancer drugs, immunosuppressants, agrochemicals and other valuable compounds, are produced by microorganisms. Many of these are biosynthesised by modular enzymatic assembly line polyketide synthases, non-ribosomal peptide synthetases, and hybrids thereof. To alter the backbone structure of these valuable but difficult to modify compounds, the respective enzymatic machineries can be engineered to create even more valuable molecules with improved properties and/or to bypass resistance mechanisms. In the past, many attempts to achieve assembly line pathway engineering failed or led to enzymes with compromised activity. Recently our understanding of assembly line structural biology, including an appreciation of the conformational changes that occur during the catalytic cycle, have improved hugely. This has proven to be a driving force for new approaches and several recent examples have demonstrated the production of new-to-nature molecules, including anti-infectives. We discuss the developments of the last few years and highlight selected, illuminating examples of assembly line engineering.

中文翻译：

---

工程化酶组装线以生产新的抗生素。

微生物产生许多重要的治疗剂，包括广泛使用的抗生素，抗癌药，免疫抑制剂，农用化学品和其他有价值的化合物。其中许多是通过模块化酶组装线聚酮化合物合成酶，非核糖体肽合成酶及其杂化体生物合成的。为了改变这些有价值但难以修饰的化合物的主链结构，可以设计相应的酶机制以产生具有改进的性质的甚至更有价值的分子和/或绕开抗性机制。过去，实现组装线途径工程的许多尝试失败或导致酶的活性受损。最近我们对流水线结构生物学的理解，包括对催化循环过程中发生的构象变化的认识，已大大改善。事实证明，这是新方法的驱动力，最近的几个例子证明了生产包括抗感染药在内的新自然分子的过程。我们讨论了最近几年的发展，并重点介绍了一些选定的例子，这些例子阐明了流水线工程的实例。