Plant-endophyte associations: Rich yet under-explored sources of novel bioactive molecules and applications

Diverse forms of plant-microbe associations affect agriculture and the environment. Both plants and microbes have evolved to produce a variety of proteins and metabolites to enable or modulate their interaction with other organisms and modify their surrounding environments. Some such high-value metabolites produced by endophytes have been widely used as pharmaceutical agents and for socio-economic applications. Rapid advances in genomics have enabled the elucidation of the biology and ecology of endophytes, including their metabolic potential, by deciphering their genomic blueprints and investigating how they perform specific functions in various environmental and ecological contexts. Herein, we review recent advances in understanding the biology and ecology of endophytes and how this understanding has been harnessed to support agricultural sustainability, improve environmental health, and produce new metabolites of therapeutic significance. Genetic engineering of endophytes, guided by an enhanced understanding of their biology and advances in gene manipulation tools, promises to facilitate the production of "value-added" metabolites and the application of endophytes to solve agricultural and environmental problems. However, several knowledge deficiencies in endophyte biology should be remedied to realize their maximum potential.