Computational and experimental tools for the discovery, design and heterologous production of secondary metabolites. (a) BGC mining in sequenced fungal genomes, combined with untargeted metabolomics approaches, are unlocking the chemical diversity harbored in major fungal lineages. With known libraries of gene cluster families, BGCs and specific metabolites can be linked and verified through downstream genetic approaches. (b) Genome-scale modeling guides rational design of organisms to achieve desirable metabolite flux into the target product. Omics data (e.g. Tn-seq, transcriptomics, proteomics and metabolomics) can be integrated into model construction to improve the mapping accuracy of the core metabolism and constrain the flux at each reaction. (c) Scalable platforms for selecting the optimal host for heterologous production.