Induction of Secondary Metabolites from the Marine-Derived Fungus Aspergillus versicolor through Co-cultivation with Bacillus subtilis

Nada M. Abdel-Wahab; Sebastian Scharf; Ferhat C. Özkaya; Tibor Kurtán; Attila Mándi; Mostafa A. Fouad; Mohamed S. Kamel; Werner E. G. Müller; Rainer Kalscheuer; Wenhan Lin; Georgios Daletos; Weaam Ebrahim; Zhen Liu; Peter Proksch

doi:10.1055/a-0835-2332

Planta Medica, Inhaltsverzeichnis

Planta Med 2019; 85(06): 503-512
DOI: 10.1055/a-0835-2332

Natural Product Chemistry and Analytical Studies

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Induction of Secondary Metabolites from the Marine-Derived Fungus Aspergillus versicolor through Co-cultivation with Bacillus subtilis

Nada M. Abdel-Wahab^*

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

²Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt

,

Sebastian Scharf^*

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

,

Ferhat C. Özkaya

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

,

Tibor Kurtán

³Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary

,

Attila Mándi

³Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary

,

Mostafa A. Fouad

²Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt

,

Mohamed S. Kamel

²Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt

⁴Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia, Egypt

,

Werner E. G. Müller

⁵Institut für Physiologische Chemie, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Mainz, Germany

,

Rainer Kalscheuer

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

,

Wenhan Lin

⁶State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China

,

Georgios Daletos

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

,

Weaam Ebrahim

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

⁷Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

,

Zhen Liu

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

,

Peter Proksch

¹Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

› Institutsangaben

Abstract

A new cyclic pentapeptide, cotteslosin C (1), a new aflaquinolone, 22-epi-aflaquinolone B (3), and two new anthraquinones (9 and 10), along with thirty known compounds (2, 4 – 8, 11 – 34) were isolated from a co-culture of the sponge-associated fungus Aspergillus versicolor with Bacillus subtilis. The new metabolites were only detected in the co-culture extract, but not when the fungus was grown under axenic conditions. Furthermore, the co-culture extract exhibited an enhanced accumulation of the known constituents versicolorin B (14), averufin (16), and sterigmatocyctin (19) by factors of 1.5, 2.0, and 4.7, respectively, compared to the axenic fungal culture. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and mass spectrometry as well as by comparison with literature data. The absolute configuration of compounds 3, 9, and 10 was determined by ECD (electronic circular dichroism) analysis aided by TDDFT-ECD (time-dependent density functional theory electronic circular dichroism) calculations. Compounds 15, 18 – 21, and 26 exhibited strong to moderate cytotoxic activity against the mouse lymphoma cell line L5178Y, with IC₅₀ values ranging from 2.0 to 21.2 µM, while compounds 14, 16, 31, 32, and 33 displayed moderate inhibitory activities against several gram-positive bacteria, with MIC values ranging from 12.5 to 50 µM.

Key words

sponge-derived fungus - Aspergillus versicolor - cyclic pentapeptide - co-culture - ECD calculations - cytotoxicity - antibacterial activity

Volltext

Referenzen

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