Fungal endophytes from anticancer plants as producers of the antitumor agent l-asparaginase: A look at diversity, ubiquity, and enzyme production

Abstract

Endophytes are microorganisms inhabiting plants without causing any visible symptoms. In recent years, endophytes from medicinal or anticancer plants have demonstrated the ability to produce bioactive compounds similar to anticancer compounds derived from their host plant, i.e., taxol from Taxomyces andreanae found in the Pacific yew tree. In this study, we explored endophytes from several common medicinal plants for their potential to produce L-asparaginase, an anticancer agent that deprives tumor cells from L-asparagine. The plants selected have been documented for their ethnobotanical anticancer properties, which include Cymbopogon citratus, Murraya koenigii, Oldenlandia diffusa, Pereskia bleo, and Andrographis paniculata. The fungal endophytes were isolated and identified and their L-asparaginase production was determined. Results revealed that anticancer plants do harbor a diverse group of fungal endophytes, and their distribution and relative abundance vary according to plant parts (roots, stem, leaves). The number of endophytes isolated is highest from A. paniculata (50 isolates), followed by P. bleo (40 isolates), O. diffusa (25 isolates), C. citratus (14 isolates), and M. koenigii (10 isolates). Most of the fungal endophytes are species of Colletotrichum, Fusarium, Penicillium, Phoma, and Aspergillus. Comparison of the species diversity in each plant part showed that roots typically harbor the most number of endophytes isolated, followed by leaf or stem tissues. Nevertheless, the number of isolates with L-asparaginase production differs among plants. A. paniculata has the most number of endophytes with L-asparaginase activities (39 of the 50 isolates), compared to P. bleo, O. diffusa, C. citratus, and M. koenigii with 15, 7, 2, and 1 positive isolate(s), respectively. Their L-asparaginase activities quantified were between 0.009 and 0.0246 M-1 mL-1 min-1 of mean L-asparaginase activity, with higher levels derived from endophytes from O. diffusa. Our study has shown that endophytes from anticancer plants have the potential as producers of L-asparaginase. They can be developed for upscale production under optimized conditions, to produce sufficient L-asparaginase for cancer treatment.