Unveiling the Chemical Space of Astin‐Type Peptides in Aster Tataricus , Cyanodermella Asteris , and Talaromyces Islandicus

The plant Aster tataricus L.f. is known as the main source of astin-type cyclopentapeptides. However, recent studies have shown that the endophytic fungus Cyanodermella asteris contains a biosynthetic gene cluster (BGC) ast encoding for astin core-structure biosynthesis and that it produces three astins, namely astins C, F, and G. The foodborne fungus Talaromyces islandicus produces the structurally highly related cyclochlorotine mycotoxins encoded by the BGC cct with significant genetic homology to ast from C. asteris. We thus became interested in exploring and comparing the astin-type peptide diversity found in these three source organisms to answer the long-standing question of the true metabolic origin of the astins. Mass spectrometry-based molecular networking and fragmentation trees revealed that A. tataricus, C. asteris, and T. islandicus indeed contain many more derivatives, hence uncovering a huge peptide chemodiversity resulting from promiscuous NRPS systems regarding amino acid selectivity. Both NRPS systems produce structurally related and even a number of identical compounds. Our findings reveal comprehensive metabolic insights strongly indicating that the endophyte C. asteris is the sole producer of the astin peptide family and, contrary to previous assumptions, metabolic cross-talk with the host plant is unlikely to have a major impact on astin structural diversity.