Over 90 years have passed since Alexander Fleming's discovery of penicillin, the first recognized, naturally occurring antibiotic. Penicillin is a representative of a group of metabolites produced by large multienzyme complexes [nonribosomal peptide synthetases (NRPSs)] in a ribosome-independent fashion. Nonribosomal peptides (NRPs) are structurally diverse metabolites produced almost exclusively by bacteria and fungi. NRPs include bioactive compounds useful for pharmaceutical applications (e.g., antibiotics, antitumor compounds, and immunosuppressants) and therefore much progress has been made in our understanding of medically relevant characteristics of NRPs in the past decades. Natural roles of NRP metabolites, on the other hand, have been largely ignored, and much less is known about the biological/physiological significance of NRPs under natural settings. In the present review, we summarize past and current work on natural functions of NRPs in their fungal producers, with a focus on virulence, development, and stress tolerance, and highlight the diverse roles these small peptide metabolites play. Some NRPs are involved in interactions with host organisms, others work in fungus-environment interfaces, and still others are crucial for vegetative and reproductive development of the producing fungi.

自亚历山大·弗莱明（Alexander Fleming）发现青霉素（第一种公认的天然抗生素）以来，已有90多年的历史了。青霉素是由大型多酶复合物[非核糖体肽合成酶（NRPS）]以核糖体非依赖性方式产生的一组代谢物的代表。非核糖体肽（NRPs）是结构多样性的代谢产物，几乎仅由细菌和真菌产生。NRP包括可用于药物应用的生物活性化合物（例如抗生素，抗肿瘤化合物和免疫抑制剂），因此，在过去的几十年中，我们对NRP的医学相关特性的了解已取得了很大的进步。另一方面，NRP代谢物的天然作用已被大大忽略，人们对自然环境下NRP的生物学/生理学意义知之甚少。在本综述中，我们总结了NRP在其真菌生产者中的自然功能的过去和当前工作，重点是毒力，发育和胁迫耐受性，并着重介绍了这些小肽代谢物发挥的不同作用。一些NRP参与了与宿主生物的相互作用，其他的则参与了真菌与环境的相互作用，而另一些对生产真菌的营养和生殖发育至关重要。