Polyynes are well-known unstable secondary metabolites with various biological functions and mainly identified from plant, marine organism and fungal sources [1]. Only a few of polyynes have been identified from bacteria. The biosynthetic gene cluster (BGC) of bacterial polyyne was first revealed in 2014 [2], providing us an opportunity to explore the bacterial polyynes using genome mining approach. Through the genome mining analysis, we have found only six genus of bacteria are potential to produce polyynes. The phylogenetic analysis of bacterial polyyne BGCs demonstrated that Massilia sp. YMA4 is a unique source to produce novel polyyne structures. Since the production of polyynes from Massilia sp. YMA4 was unstable, here we employed an integrated omics approach, including RNA-seq transcriptomics, in situ metabolomics, together with gene inactivation to discover massilicins, the silent and unstable antifungal agents, from dual-culture of Massilia sp. YMA4 and Candida albicans. The click reaction was then employed to trap polyynes from Massilia sp. YMA4 extract for further isolation and structure elucidation of massilicins.
[1] Shun ALKS, Tykwinski RR. Angew Chem Int Ed 2006; 45: 1034-1057; [2] Ross C, Scherlach K, Kloss F, Hertweck C. Angew Chem Int Ed 2014; 53: 7794-7798