Isolation and biological activity of six new polyketide and terpenoid derivatives from Neopestalotiopsis Clavispora AL01.

A fungus strain, Neopestalotiopsis clavispora AL01, was isolated from the leaf spot of the plant Phoenix dactylifera. Further chemical investigation of the fermentation extract of this strain afforded six new secondary metabolites (1-6), along with 11 known compounds (7-17) which included a new natural compound (7). Their structures were determined by extensive spectroscopic analysis including one-and two-dimensional (1D and 2D) NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and ECD and NMR calculations. All compounds were evaluated for their phytotoxic activities. Among them, compounds 10, 12 and 13 exhibited phytotoxic activities against Nicotiana tabacum. Compound 3 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus, Micrococcus luteus and Vibrio harveyi. Taken collectively, these findings establish a solid research foundation for future investigations on bioactive natural products derived from phytopathogenic fungi.

P450-Modified Ribosomally Synthesized Peptides with Aromatic Cross-Links.

Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists' ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples. Herein, we developed an efficient workflow for the identification of P450-modified RiPPs in bacterial genomes, resulting in the discovery of a large number of P450-modified RiPP gene clusters. Combined with subsequent expression and structural characterization of the products, we have identified 11 novel P450-modified RiPPs with different cross-linking patterns from four distinct classes. Our results greatly expand the structural diversity of P450-modified RiPPs and provide new insights and enzymatic tools for the production of cyclic peptides.

Pleosporalins H and I, two new heptaketides from the endophytic fungus Pleosporales sp. F46 by using OSMAC strategy.

Two new heptaketides, pleosporalins H and I (1 and 2), as well as seven biosynthetically related known polyketides (3-9) were isolated from the endophytic fungus, Pleosporales sp. F46 by employing the one strain-many compounds (OSMAC) approach. The planar, relative and absolute structures of these compounds were identified by extensive spectroscopic analysis including HRMS, NMR, optical rotations and ECD calculations. The cytotoxic efficiencies of all isolated compounds 1-9 were evaluated against four cancer cell lines A549, CT-26, MCF-7 and MDA-MB-231.

Induced production of steroids by co-cultivation of two endophytes from Mahonia fortunei.

A new ergosterol derivative, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (1), and a biosynthetically related known compound, (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (2), were isolated from the co-culture between endophytic fungus Pleosporales sp. F46 and endophytic bacterium Bacillus wiedmannii Com1 both inhibiting in the medicinal plant Mahonia fortunei. The structure of the new compound 1 was determined by extensive spectroscopic analysis using HRMS and NMR, together with the modified Mosher's ester method. This is the first example of isolation of a ergosterol derivative with a Δ20(22)-double bond in the side chain. Compound 1 exhibited moderate antibacterial efficacy against Staphylococcus aureus and no obvious cytotoxic activities against the cancer cell lines A549, MDA-MB-231 and Hct116. Our results not only reveal that compound 1 is a potent antibacterial lead compound, but also highlight the powder of co-cultivation for inducing the production of cryptic natural products from endophytes derived from the same host plant.