Efficient exploration of terpenoid biosynthetic gene clusters in filamentous fungi

Terpenoids, critical components of human medicine, are the largest family natural products. Fungi an important source terpenoids, but many corresponding biosynthetic gene clusters (BGCs) silent in laboratory conditions. Strategies such as homologous activation and heterologous expression were usually used to active a single cluster, making them low efficiency. Here we developed automated high-throughput (auto-HTP) biofoundry workflow using Aspergillus oryzae chassis that enables efficient genome mining, characterization BGCs identification bioactive fungal terpenoids. We simultaneously refactored 39 into 208 engineered strains, producing 185 distinct An anti-inflammatory screen returned sesterterpenoid mangicol J; re-examination our strains revealed likely pathway. Finally, optimized mevalonate pathway A. provide more for overproduction The auto-HTP together with can accelerate discovery development terpenoid High-performance approaches fungi lacking. Now, fully is mining analysis