Three new 12- or 13-membered-ring macrocyclic alkaloids, named ascomylactams A–C (1–3), along with the analogues phomapyrrolidone C (4) and phomapyrrolidone A (5) were isolated from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. The structures and absolute configurations of 1 and 2 were determined by single-crystal X-ray diffraction experiments, which represents the first crystal structures described for a (6/5/6/5) tetracyclic skeleton fused with a 12- or 13-membered-ring macrocyclic moiety. The configurations of phomapyrrolidone C (4) and phomapyrrolidone A (5) were revised by detailed analysis of the NMR data. In a cytotoxic assay, compounds 1 and 3 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, SNB19, HCT116, NCI-H460, and PC-3 human cancer cell lines, with IC50 values in the range of 4.2–7.8 μM.

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Summary Ralstonia solanacearum , one of the most destructive plant bacterial pathogens, delivers an array of effector proteins via its type III secretion system for pathogenesis. However, the biochemical functions of most of these proteins remain unclear. RipN is a type III effector with unknown function(s) from the pathogen R. solanacearum . Here, we demonstrate that RipN is a conserved type III effector found within the R. solanacearum species complex that contains a putative Nudix hydrolase domain and has ADP‐ribose/NADH pyrophosphorylase activity in vitro . Further analysis shows that RipN localizes to the endoplasmic reticulum (ER) and nucleus in Nicotiana tabacum leaf cells and Arabidopsis protoplasts, and truncation of the C‐terminus of RipN results in a loss of nuclear and ER targeting. Furthermore, the expression of RipN in Arabidopsis suppresses callose deposition and the transcription of pathogen‐associated molecular pattern (PAMP)‐triggered immunity (PTI) marker genes under flg22 treatment, and promotes bacterial growth in planta . In addition, the expression of RipN in plant cells alters NADH/NAD + , but not GSH/GSSG, ratios, and its Nudix hydrolase activity is indispensable for such biochemical function. These results suggest that RipN acts as a Nudix hydrolase, alters the NADH/NAD + ratio of the plant and contributes to R. solanacearum virulence by suppression of PTI of the host.

Seven polyketides, including two new isochromanes, penisochromanes A and B (1 and 2), as well as five known compounds were obtained from an ascidian-derived fungus Penicillium sp. 4829. Their structures were identified by extensive spectroscopic analyses. The structures of compounds 1 and 3 were further determined by the X-ray crystallography. Compounds 1 and 2 were the first example of isochromane with three adjacent oxy substituents in natural source. Compound 4 exhibited selective activities against two Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, with MIC values 6.25 and 12.5 μM, respectively.