Unser 10. Leibniz Plant Biochemistry Symposium am 7. und 8. Mai war ein großer Erfolg. Thematisch ging es in diesem Jahr um neue Methoden und Forschungsansätze der Naturstoffchemie. Die exzellenten Vorträge über Wirkstoffe…
Omanische Heilpflanze im Fokus der Phytochemie IPB-Wissenschaftler und Partner aus Dhofar haben jüngst die omanische Heilpflanze Terminalia dhofarica unter die phytochemische Lupe genommen. Die Pflanze ist reich an…
Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Plant immunity is a multilayered process that includes recognition of patterns or effectors from pathogens to elicit defense responses. These include the induction of a cocktail of defense metabolites that typically restrict pathogen virulence. Here, we investigate the interaction between barley roots and the fungal pathogens Bipolaris sorokiniana (Bs) and Fusarium graminearum (Fg) at the metabolite level. We identify hordedanes, a previously undescribed set of labdane-related diterpenoids with antimicrobial properties, as critical players in these interactions. Infection of barley roots by Bs and Fg elicits hordedane synthesis from a 600-kb gene cluster. Heterologous reconstruction of the biosynthesis pathway in yeast and Nicotiana benthamiana produced several hordedanes, including one of the most functionally decorated products 19-b-hydroxy-hordetrienoic acid (19-OH-HTA). Barley mutants in the diterpene synthase genes of this cluster are unable to produce hordedanes but, unexpectedly, show reduced Bs colonization. By contrast, colonization by Fusarium graminearum, another fungal pathogen of barley and wheat, is 4-fold higher in the mutants completely lacking hordedanes. Accordingly, 19-OH-HTA enhances both germination and growth of Bs, whereas it inhibits other pathogenic fungi, including Fg. Analysis of microscopy and transcriptomics data suggest that hordedanes delay the necrotrophic phase of Bs. Taken together, these results show that adapted pathogens such as Bs can subvert plant metabolic defenses to facilitate root colonization.
Publikation
Lam, Y. T. H.; Hoppe, J.; Dang, Q. N.; Porzel, A.; Soboleva, A.; Brandt, W.; Rennert, R.; Hussain, H.; Davari, M. D.; Wessjohann, L.; Arnold, N.;Purpurascenines A–C, azepino-indole alkaloids from Cortinarius purpurascens: Isolation, biosynthesis, and activity studies on the 5-HT2A receptorJ. Nat. Prod.861373-1384(2023)DOI: 10.1021/acs.jnatprod.2c00716
Three previously undescribed azepino-indole alkaloids, named purpurascenines A−C (1−3), together with the new-to-nature 7-hydroxytryptophan (4) as well as two known compounds, adenosine (5) and riboflavin (6), were isolated from fruiting bodies of Cortinarius purpurascens Fr. (Cortinariaceae). The structures of 1−3 were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivo experiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1 was analyzed using 1D NMR and HRESIMS methods. With [3-13C]-pyruvate, a dramatic enrichment of 13C was observed, and hence a biosynthetic route via a direct Pictet−Spengler reaction between α-keto acids and 7-hydroxytryptophan (4) is suggested for the biosynthesis of purpurascenines A−C (1−3). Compound 1 exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silico docking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2A serotonin receptor’s active site. A new functional 5-HT2A receptor activation assay showed no functional agonistic but some antagonistic effects of 1 against the 5-HT-dependent 5-HT2A activation and likely antagonistic effects on putative constitutive activity of the 5-HT2A receptor.
Publikation
Hussain, H.; Xiao, J.; Ali, A.; Green, I. R.; Westermann, B.;Unusually cyclized triterpenoids: occurrence, biosynthesis and chemical synthesisNat. Prod. Rep.40412-451(2023)DOI: 10.1039/d2np00033d
Covering: 2009 to 2021Biosynthetically, most of the syntheses of triterpenes follow the cascade cyclization and rearrangement of the acyclic precursors viz., squalene (S) and 2,3-oxidosqualene (OS), which lead to the very well known tetra- and pentacyclic triterpene skeletons. Aside from these, numerous other triterpenoid molecules are also reported from various natural sources and their structures are derived from \"S\" and \"OS\" via some unusual cyclization operations which are different from the usual tetra- and pentacyclic frameworks. Numerous compelling advances have been made and reported in the identification of these unusual cyclized mono-, di-, tri- and tetracyclic triterpenes between 2009 and 2021. Besides a dramatic increase in the newly isolated uncommon cyclized triterpenoids, substantial progress in the (bio)-synthesis of these triterpenes has been published along with significant progress in their biological effects. In this review, 180 new unusual cyclized triterpenoids together with their demonstrated biogenetic pathways, syntheses and biological effects will be categorized and discussed.
Publikation
Hussain, H.; Siddiqui, H.; Gerothanassis, I. P.;Prof. Dr. M. Iqbal Choudhary-A lifetime career dedicated to remarkable services in “natural products sciences”Frontiers in Pharmacology141119419(2023)DOI: 10.3389/fphar.2023.1119419