Utilizing cross-species co-cultures for discovery of novel natural products.

• Cross-species co-cultures can be used to activate cryptic genes' expression for biosynthesis of novel natural products. • A variety of co-cultivation methods have been established for cross-species microbial co-cultures. • Identification of co-culture-activated cryptic genes and the associated biosynthesis pathways is challenging. Discovery of new natural products, especially those with high biological activities and application values, is of great research significance. However, conventional methods based on the cultivation of microbial mono-cultures can hardly satisfy the increasing need of novel natural product generation. Recently, the development of co-cultures composed of different species has emerged as an effective approach for mining novel natural products. Inspired by microbial communities in nature, these co-culture systems create favorable environmental conditions to promote interactions between co-culture members for activating the natural product biosynthesis that is hard to induce otherwise. A large variety of novel natural products have been identified using this robust approach. This review summarizes the recent achievements of using cross-species co-cultures for natural products discovery and discusses the existing challenges and future directions. [ABSTRACT FROM AUTHOR]