Serine-glycine-betaine, a novel dipeptide from an endophyte Macrophomina phaseolina: isolation, bioactivity and biosynthesis.

Abstract

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. 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 <20µgml-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 15·16μmoll-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). A novel di-peptide, serine-glycine-betaine isolated from M. phaseolina induced apoptosis in MIA-Pa-Ca-2 cells. This study confirms that dipeptides like serine-glycine-betaine and tyrosine-betaine might be specific to fungal genera, hence being used for diagnostic purposes.