Endophytic Streptomyces: an underexplored source with potential for novel natural drug discovery and development

Streptomyces has long been considered as key sources for natural compounds discovery in medicine and agriculture. These compounds have been demonstrated to possess different biological activities, including antibiotic, antifungal, anticancer, and antiviral effects. As a result, new pharmaceuticals and antibiotics have been developed. Nevertheless, there have been only a few novel discoveries of bioactive compounds in the past decades from Streptomyces in natural habitats. There is, therefore, now a renewed search for new Streptomyces species having the potential to produce many compounds from one strain in lesser explored natural habitats that may be helpful in fighting diseases. Consequently, modern genome mining approaches are imperative for discovering structurally novel natural compounds with therapeutic applications from untapped sources. In light of these facts, endophytic Streptomyces from plants may offer new avenues for the discovery of bioactive compounds with distinctive chemical properties and activities. In the present review, we present the progress made in isolating natural compounds from endophytic Streptomyces originating from plants which have remarkable antimicrobial, cytotoxic, and antifungal properties. A different of distinct structural classes of compounds were reported from endophytic Streptomyces, such as indolosequiterpene, macrolides, flavones, peptides, naphthoquinones, and terpenoids. Further, we discussed modern genomics progress in finding biosynthetic gene clusters (BGCs) encoding compounds. Overall, this review might provide valuable insights into the potential for novel drug discovery from untapped endophytic Streptomyces in the future.