Although South Africa is known as one of the most biodiverse countries in the world, based on its unique plants and animals, microorganisms have received much less attention. Microorganisms in general and actinobacteria in particular are an underexplored source of new medicines. Recent studies have demonstrated the presence of diverse cultivable actinobacteria from various biomes. However, investigations of the natural product diversity associated with these microorganisms are lacking. We hereby present a review of natural products isolated from South African actinobacteria together with their biological activities. Many of these natural products are structurally novel and include compounds belonging to the following classes: anthraquinones, isoflavonoids, ketolides, macrolides, macrolactams, tripeptides and depsipeptides. They show a wide range of biological activities including antibacterial, antifungal, cytotoxic and antitumour activities. Significance: This review highlights the importance of actinobacteria in the discovery of new medicines and summarises the state-of-the-art on their research in South Africa. We reveal a gap in the exploitation of this resource and emphasise the opportunities for multidisciplinary research.

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