Aplospojaveedins A-C, unusual sulfur-containing alkaloids produced by the endophytic fungus Aplosporella javeedii using OSMAC strategy

Ying Gao; Marian Frank; Nicole Teusch; Dennis Woschko; Christoph Janiak; Attila Mándi; Tibor Kurtán; Rudolf Hartmann; Katja Schiedlauske; Lasse van Geelen; Rainer Kalscheuer; Jesko Kaiser; Christoph G W Gertzen; Holger Gohlke; Bin-Gui Wang; Peter Proksch; Zhen Liu

doi:10.3389/fmicb.2024.1458622

Aplospojaveedins A-C, unusual sulfur-containing alkaloids produced by the endophytic fungus Aplosporella javeedii using OSMAC strategy

Front Microbiol. 2024 Sep 27:15:1458622. doi: 10.3389/fmicb.2024.1458622. eCollection 2024.

Authors

Ying Gao^{1

2}, Marian Frank², Nicole Teusch², Dennis Woschko³, Christoph Janiak³, Attila Mándi⁴, Tibor Kurtán⁴, Rudolf Hartmann⁵, Katja Schiedlauske², Lasse van Geelen², Rainer Kalscheuer², Jesko Kaiser⁶, Christoph G W Gertzen⁶, Holger Gohlke^{6

7}, Bin-Gui Wang⁸, Peter Proksch², Zhen Liu¹

Affiliations

¹ Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.
² Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University, Düsseldorf, Germany.
³ Institute of Inorganic and Structural Chemistry, Heinrich Heine University, Düsseldorf, Germany.
⁴ Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary.
⁵ Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich GmbH, Jülich, Germany.
⁶ Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany.
⁷ Institute of Bio- and Geosciences (IBG-4: Bioinformatics), Forschungszentrum Jülich GmbH, Jülich, Germany.
⁸ CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

Abstract

Three sulfur-containing alkaloids aplospojaveedins A-C (1-3) with a hitherto undescribed carbon skeleton comprising octahy-dronaphthalene, α, β-unsaturated lactam and glycine-cysteine moieties were isolated from Aplosporella javeedii. Their structures were elucidated by 1D and 2D NMR spectroscopy, HR-MS, X-ray diffraction analysis, DFT-NMR and TDDFT-ECD calculations. A plausible biosynthetic pathway and putative targets are described. The blind docking suggested that 1-3 may have functional effects on several putative targets such as the GPCR cannabinoid receptor 2 or the integrin α5β1 complex.

Keywords: Aplosporella javeedii; DFT-NMR calculations; OSMAC approach; TDDFT-ECD calculations; X-ray diffraction; alkaloids; target prediction.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The Bruker diffractometer was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under grant INST 208/589–1. TK and AM are grateful the National Research Development and Innovation Office (grant nos. K-138672 and FK-134653) for financial support. The CPU time from the Governmental Information Technology Development Agency (KIFÜ) is gratefully acknowledged. This work was supported in part by the Deutsche Forschungsgemeinschaft [DFG, German Research Foundation; 270650915/GRK 2158 (to HG, RK, PP)]. HG is grateful for computational support and infrastructure provided by the “Zentrum für Informations-und Medientechnologie” (ZIM) at the Heinrich Heine University Düsseldorf and the computing time provided by the John von Neumann Institute for Computing (NIC) to HG on the supercomputer JUWELS at Jülich Supercomputing Center (JSC; user ID: VSK33). ZL thanks Hunan Provincial Natural Science Foundation of China (2022JJ40286), the Changsha Municipal Natural Science Foundation (kq2202257), and Intra Institutional Open Fund of School of Medicine, Hunan Normal University (KF2022001) for support.