Abstract
BackgroundSecondary fungal metabolites are important sources for new drugs against infectious diseases and cancers.MethodsTo obtain a library with enough diversity, we collected about 2,395 soil samples and 2,324 plant samples from 36 regions in Africa, Asia, and North America. The collection areas covered various climate zones in the world. We examined the usability of the global fungal extract library (GFEL) against parasitic malaria transmission, Gram-positive and negative bacterial pathogens, and leukemia cells.ResultsNearly ten thousand fungal strains were isolated. Sequences of nuclear ribosomal internal transcribed spacer (ITS) from 40 randomly selected strains showed that over 80% were unique. Screening GFEL, we found that the fungal extract from Penicillium thomii was able to block Plasmodium falciparum transmission to Anopheles gambiae, and the fungal extract from Tolypocladium album was able to kill myelogenous leukemia cell line K562. We also identified a set of candidate fungal extracts against bacterial pathogens.
Highlights
Natural products, produced by living organisms in nature, have been used as medicine for thousands of years (Dias, Urban & Roessner, 2012; Buyel, 2018)
Yield of many target fungal secondary metabolites is restricted by fungal growth and differentiation (Nielsen & Nielsen, 2017; Keller, 2019; Pham et al, 2019), which is resolved by new technologies that enable us to engineer a fungus to produce a specific compound in high yield by modifying its metabolic pathways (Van Dijk & Wang, 2016)
After removal of the blocking solution, fibrinogen-related protein 1 (FREP1) (10 μg/mL) in blocking buffer (PBS plus 0.2% bovine serum albumin (BSA)) was added to each well, and 1 μL fungal extract was taken from a 96-well plate containing 2 mg/mL crude extract dissolved in dimethyl sulfoxide (DMSO) in each well with a multiple-channel pipette and transferred to the ELISA plate, incubated for 1 hr at room temperature (RT) with gentle shaking
Summary
Natural products, produced by living organisms in nature, have been used as medicine for thousands of years (Dias, Urban & Roessner, 2012; Buyel, 2018). A diverse global fungal library for drug discovery. Fungi produce broad and diverse secondary metabolites with a vast difference in chemical structures (Pham et al, 2019). Yield of many target fungal secondary metabolites is restricted by fungal growth and differentiation (Nielsen & Nielsen, 2017; Keller, 2019; Pham et al, 2019), which is resolved by new technologies that enable us to engineer a fungus to produce a specific compound in high yield by modifying its metabolic pathways (Van Dijk & Wang, 2016). The endophytic fungi from the plants can generate similar secondary metabolites as their hosts (Venieraki, Dimou & Katinakis, 2017). We focus on generating a global diverse fungal library to facilitate new drug discovery.
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