Comparative bioactive compound profiling of endophytic fungi and their respective host plants for sustainable drug discovery

Medicinal plants have been serving as the foundation of traditional medicine, offering a vast reservoir of bioactive compounds with diverse therapeutic potential. In recent decades, the symbiotic association between plants and their endophytic fungi has emerged as a paradigm for novel natural product biosynthesis and sustainable pharmaceutical production. This review critically examines the parallel and complementary production of bioactive metabolites by medicinal plants and their endophytes, addressing problems in scalability of bioactive compounds. Advances in molecular techniques and genomic tools have expanded our ability to predict and characterize biosynthetic gene clusters (BGCs), linking genetic potential to chemical diversity. Integrative omics approaches, coupled with synthetic biology tools such as CRISPR-Cas9 mediated activation, heterologous expression, and bioprocess optimization, offer promising strategies to overcome scaleup barriers. • Critically compares metabolic mimicry between medicinal plants and fungal endophytes. • Addresses biosynthetic silencing and strain instability as barriers to scalability. • Evaluates BGC prediction and multi-omics for characterizing chemical diversity. • Highlights CRISPR-Cas9 and synthetic biology for activating cryptic pathways. • Proposes a framework for transitioning endophytes to industrial bio-factories.