A Molecular Networking Based Discovery of Diketopiperazine Heterodimers and Aspergillicins from Aspergillus caelatus

Abstract

The number of species in Aspergillus section Flavi has recently increased to 36 and includes some of the most important and well-known species in the genus Aspergillus. Numerous secondary metabolites, especially mycotoxins, have been reported from species such as A. flavus; however many of the more recently described species are less studied from a chemical point of view. This paper describes the use of MS/MS-based molecular networking to investigate the metabolome of A. caelatus leading to the discovery of several new diketopiperazine dimers and aspergillicins. An MS-guided isolation procedure yielded six new compounds, including asperazines D–H (1–5) and aspergillicin H (6). Asperazines G and H are artifacts derived from asperazines E and F formed during the separation process by formic acid. Two known compounds, aspergillicins A and C (7 and 8), were isolated from the same strain. Structures were elucidated by analyzing their HR-MS/MS and NMR spectroscopic data. The absolute configuration of asperazines D–F and aspergillicin H were deduced from the combination of NMR, Marfey’s method, and ECD analyses.

An integrated strategy for the comprehensive profiling of the chemical constituents of Aspongopus chinensis using UPLC-QTOF-MS combined with molecular networking

“… 2022 ; Wang et al. 2022 ). Finally, the MS/MS spectra were compared pairwise to search for spectral similarities, including the same fragment ions and/or neutral losses.…”

“… 2022 ; Wang et al. 2022 ). The MN combined with UPLC-QTOF-MS is mostly used to analyze the metabolic components of fungi and one type of components in plants used in traditional Chinese medicines (TCMs) (Messaili et al.…”

Biosynthesis of pyrroloindoline-containing natural products

“…172 These homologous loci all bear the three characteristic genes, specically, the CDPS-encoding gene dmtB, the prenyltransferase (PT)-encoding gene dmtC and the membranebound terpene cyclase (TC)-encoding gene dmtA. Through heterologous expression, gene inactivation and biochemical assays, they veried that DmtC1 is indeed a phytoene-synthaselike (PSL) family prenyltransferase, which could transform the farnesyl diphosphate (FPP) moiety to cW L -V L (193), cW L -P L (86), and cW L -L L (192), leading to the production of pre-drimentine G (196), pre-drimentine C (195) and pre-drimentine A (194), respectively. Subsequently, these pre-drimentines could be 138), respectively (Fig.…”

“…193 Recently, asperazine D ( 221) and E (219), two other novel analogs of asperazine, were discovered from A. caelatus (IBT 21091); however, they did not display obvious activity against the HepG2 and CaSki cell lines and a few of the tested fungal strains. 194 Ditryptophenaline (13) (Section 6.1.1) isolated from Aspergillus avus has a similar chemical structure with asperazines and pestalazines. Its BGC, containing three genes of NRPS (dtpA), MT (dptB) and cytochrome P450 (dptC), provides some key information to trace the gene clusters responsible for asperazines and pestalazines.…”

“…It was discovered from the secondary metabolites of the plant pathogenic fungus Pestalotiopsis theae. 191 Subsequently, two other products, asperazine A (11) and asperazine F (224), were isolated from an endophytic fungus A. niger 208 and A. caelatus IBT 21091, 194 respectively. Besides asperazine A (11) showing weak cytotoxicity against the A2780 cell line, the other products had no other obvious bioactivity.…”