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Planta Med 2020; 86(13/14): 988-996
DOI: 10.1055/a-1130-4856
Biological and Pharmacological Activity
Original Papers

Drug Leads from Endophytic Fungi: Lessons Learned via Scaled Production

Tyler N. Graf
1   Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA
,
Diana Kao
1   Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA
,
José Rivera-Chávez
1   Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA
2   Department of Natural Products, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Jacklyn M. Gallagher
1   Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA
,
Huzefa A. Raja
1   Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA
,
Nicholas H. Oberlies
1   Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA
› Author AffiliationsSupported by: National Center for Complementary and Integrative Health F31 AT009264
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Abstract

Recently, the isolation and elucidation of a series of polyhydroxyanthraquinones were reported from an organic extract of a solid phase culture of an endophytic fungus, Penicillium restrictum (strain G85). One of these compounds, ω-hydroxyemodin (1), showed promising quorum-sensing inhibition against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in both in vitro and in vivo models. The initial supply of 1 was 19 mg, and this amount needed to be scaled by a factor of 30 to 50 times, in order to generate material for further in vivo studies. To do so, improvements were implemented to enhance both the fermentation of the fungal culture and the isolation of this compound, with the target of generating > 800 mg of study materials in a period of 13 wk. Valuable insights, both regarding chemistry and mycology, were gained during the targeted production of 1 on the laboratory-scale. In addition, methods were modified to make the process more environmentally friendly by judicious choice of solvents, implementing procedures for solvent recycling, and minimizing the use of halogenated solvents.

Key words

Penicillium restrictum Aspergillaceae - polyhydroxyanthraquinone - ω-hydroxyemodin - Silybum marianum Asteraceae - fungal endophyte

Supporting Information

    Structures of the polyhydroxyanthraquinones, photographs of various media studies, chromatographic analysis of samples, NMR data, schematics that outline the purification protocols, and an example extraction procedure are included in Supporting Information.

  • Supporting Information


Publication History

Received: 22 January 2020

Accepted after revision: 03 March 2020

Article published online:
26 March 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

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