Plant nucleotide binding/leucine-rich repeat (NLR) immune receptors are activated by pathogen effectors to trigger host defenses and cell death. Toll-interleukin 1 receptor domain NLRs (TNLs) converge on the ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) family of lipase-like proteins for all resistance outputs. In Arabidopsis (Arabidopsis thaliana) TNL-mediated immunity, AtEDS1 heterodimers with PHYTOALEXIN DEFICIENT4 (AtPAD4) transcriptionally induced basal defenses. AtEDS1 uses the same surface to interact with PAD4-related SENESCENCE-ASSOCIATED GENE101 (AtSAG101), but the role of AtEDS1-AtSAG101 heterodimers remains unclear. We show that AtEDS1-AtSAG101 functions together with N REQUIRED GENE1 (AtNRG1) coiled-coil domain helper NLRs as a coevolved TNL cell death-signaling module. AtEDS1-AtSAG101-AtNRG1 cell death activity is transferable to the Solanaceous species Nicotiana benthamiana and cannot be substituted by AtEDS1-AtPAD4 with AtNRG1 or AtEDS1-AtSAG101 with endogenous NbNRG1. Analysis of EDS1-family evolutionary rate variation and heterodimer structure-guided phenotyping of AtEDS1 variants and AtPAD4-AtSAG101 chimeras identify closely aligned ɑ-helical coil surfaces in the AtEDS1-AtSAG101 partner C-terminal domains that are necessary for reconstituted TNL cell death signaling. Our data suggest that TNL-triggered cell death and pathogen growth restriction are determined by distinctive features of EDS1-SAG101 and EDS1-PAD4 complexes and that these signaling machineries coevolved with other components within plant species or clades to regulate downstream pathways in TNL immunity.

Plants utilise intracellular nucleotide-binding, leucine-rich repeat (NLR) immune receptors to detect pathogen effectors and activate local and systemic defence. NRG1 and ADR1 “helper” NLRs (RNLs) cooperate with enhanced disease susceptibility 1 (EDS1), senescence-associated gene 101 (SAG101) and phytoalexin-deficient 4 (PAD4) lipase-like proteins to mediate signalling from TIR domain NLR receptors (TNLs). The mechanism of RNL/EDS1 family protein cooperation is not understood. Here, we present genetic and molecular evidence for exclusive EDS1/SAG101/NRG1 and EDS1/PAD4/ADR1 co-functions in TNL immunity. Using immunoprecipitation and mass spectrometry, we show effector recognition-dependent interaction of NRG1 with EDS1 and SAG101, but not PAD4. An EDS1-SAG101 complex interacts with NRG1, and EDS1-PAD4 with ADR1, in an immune-activated state. NRG1 requires an intact nucleotide-binding P-loop motif, and EDS1 a functional EP domain and its partner SAG101, for induced association and immunity. Thus, two distinct modules (NRG1/EDS1/SAG101 and ADR1/EDS1/PAD4) mediate TNL receptor defence signalling.

Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I.

Five new fungal hybrid polyketides, cladosins A-D (1-4), that contain a novel linear 6(3)-enamino-8,10-dihydroxy-tetraketide (1 and 2) or 6-enamino-7(8)-en-10-ol (3 and 4) moiety, as well as the biogenetically related cladosin E (5), were isolated from the deep-sea-derived fungus Cladosporium sphaerospermum 2005-01-E3. Their structures (1-5) were elucidated through a combination of spectroscopic data, chemical conversion, and both Mosher's and Marfey's methods for stereochemical assignment. A plausible biogenetic pathway to 1-5 is proposed. Cladosin C (3) possesses mild anti-influenza A H1N1 virus activity.

Two new meroterpenoids, arisugacins I (1) and J (2), together with five known meroterpenoids including arisugacin B (3), arisugacin F (4), arisugacin G (5), territrem B (6) and territrem C (7) were isolated from an endophytic fungus Penicillium sp. SXH-65. Their structures were determined by extensive spectroscopic experiments and comparison with literature data. Their cytotoxicities were evaluated against Hela, HL-60 and K562 cell lines, and only 3 and 4 exhibited weak cytotoxicities against Hela, HL-60 and K562 cell lines with IC50 values ranging from 24 to 60 μM.