Genomic insights into dendrobine biosynthesis in the endophytic fungus Fusarium sp. DN689

Dendrobine is a bioactive sesquiterpene alkaloid from Dendrobium nobile with notable pharmacological properties, yet its sustainable production remains challenging. Here, we focused on an endophytic fungal isolate, Fusarium sp. DN689, from Dendrobium nobile and confirmed its capacity for consistent dendrobine production under liquid fermentation conditions. Whole genome sequencing and mining of DN689 identified 13 terpenoid biosynthetic gene clusters, including genes of the core mevalonate (MVA) pathway as well as downstream tailoring enzymes. Furthermore, quantitative PCR revealed that the expression of four candidate cyclase and oxidase genes was positively correlated with dendrobine accumulation. Among these, a sesquiterpene cyclase encoded by one candidate gene was identified as a key enzyme in the biosynthetic pathway. Collectively, this work provides the first genomic framework for fungal dendrobine biosynthesis, and lays a foundation for future metabolic engineering and sustainable production of this valuable compound.