Induction of Diverse Cryptic Fungal Metabolites by Steroids and Channel Blockers. Author Seoung Lee, Mohammad Seyedsayamdost Publication Year 2022 Type Journal Article Abstract Fungi offer a deep source of natural products but remain underutilized. Most biosynthetic gene clusters (BGCs) that can be detected are silent or "cryptic" in standard lab cultures and their products are thus not interrogated in routine screens. As genetic alterations are difficult and some strains can only be grown on agar, we have herein applied an agar-based high-throughput chemical genetic screen to identify inducers of fungal BGCs. Using R. solani and S. sclerotiorum as test cases, we report 13 cryptic metabolites in four compound groups, including sclerocyclane, a natural product with a novel scaffold. Steroids were the best elicitors and follow-up studies showed that plant-steroids trigger sclerocyclane synthesis, which shows antibiotic activity against B. plantarii, an ecological competitor of S. sclerotiorum. Our results open new paths to exploring the chemical ecology of fungal-plant interactions and provide a genetics-free approach for uncovering cryptic fungal metabolites. Keywords Anti-Bacterial Agents, Multigene Family, Biological Products, Agar, Steroids Journal Angew Chem Int Ed Engl Volume 61 Issue 29 Pages e202204519 Date Published 2022 Jul 18 ISSN Number 1521-3773 DOI 10.1002/anie.202204519 Alternate Journal Angew Chem Int Ed Engl PMCID PMC9276648 PMID 35509119 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML