期刊
JOURNAL OF APPLIED MICROBIOLOGY
卷 131, 期 2, 页码 756-767出版社
OXFORD UNIV PRESS
DOI: 10.1111/jam.14995
关键词
apoptosis; cytotoxicity; endophytic fungus; Macrophomina phaseolina; MIA-Pa-Ca-2 cells; ROS generation
资金
- DBT, Govt. of India [BT/PR4669/PBD/17/784/2012]
- CSIR
- ICMR
This study isolated a novel dipeptide, serine-glycine-betaine, from the endophyte Macrophomina phaseolina associated with Brugmansia aurea L., which exhibited activity against human cancer cells by inducing apoptosis. Genomic analysis revealed the potential biosynthesis pathway of serine-glycine-betaine. The findings suggest dipeptides like serine-glycine-betaine and tyrosine-betaine may be specific to fungal genera and could be used for diagnostic purposes.
Aims: Endophytes are a rich source for structurally complex chemical scaffolds with interesting biological activities. Endophytes associated with Brugmansia aurea L. (family: Solanaceae), a medicinal plant, have not yet explored for the bioactive metabolites. Method and Results: Hence, Macrophomina phaseolina, a fungal endophyte, was isolated from the roots of the plant. Its methanolic extract was found active against human cancer cell lines with IC50 <20 mu g ml(-1). Later, a di-peptide compound, serine-glycine-betaine, was isolated and characterized. Serine-glycine-betaine consists of a unit of an N-trimethyl glycine attached to serine. It exhibited potent activity against MIA PaCa-2 and HCT-116 cell lines with IC50 8.9 and 15.16 mu mol l(-1), respectively. Furthermore, it induced apoptosis in MIA PaCa-2 cells confirmed by microscopy. The apoptotic cell death in MIA PaCa-2 cells was evidenced biochemically with the generation of intracellular reactive oxygen species level and leading to loss of mitochondrial membrane potential due to activation of the intrinsic pathway. This study describes the plausible biosynthesis of serine-glycine-betaine based on genomics (genome sequencing, annotation and genes alignment). Conclusions: A novel di-peptide, serine-glycine-betaine isolated from M. phaseolina induced apoptosis in MIA-Pa-Ca-2 cells. Significance and Impact of the Study: This study confirms that dipeptides like serine-glycine-betaine and tyrosine-betaine might be specific to fungal genera, hence being used for diagnostic purposes.
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