Synthetic biology based construction of fungal diterpenoid pyrone library

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach to translate tremendous amount of genomic information to richly diverse natural products in the post-genomic era. In addition, this approach increases the opportunities to rationally access not only novel skeletal natural products but also new structural analogues of bioactive natural products. For example, the reconstruction of cryptic biosynthetic pathways in heterologous hosts may discover novel natural products, while pathways that are related to those of bioactive natural products lead to access to their natural analogues. In addition, pathway redesign for combinatorial biosynthesis in heterologous hosts enables access to natural product congeners that are not programmed in nature. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs),which are potential sources of pharmaceutically beneficial natural products.