Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Academy of Scientific and Innovative Research (AcSIR), CSIR, New Delhi, India.
J Appl Microbiol. 2021 Aug;131(2):756-767. doi: 10.1111/jam.14995. Epub 2021 Feb 1.
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 IC <20 µg ml . 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 IC 8·9 and 15·16 μmol l , 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.
内生菌是具有有趣生物活性的结构复杂化学支架的丰富来源。尚未探索与药用植物布鲁格曼氏黄花（茄科）相关的内生菌的生物活性代谢产物。
因此，从植物根部分离出真菌内生菌 Macrophomina phaseolina。其甲醇提取物对人癌细胞系具有活性，IC <20 µg ml 。后来，分离并鉴定出一种二肽化合物，丝氨酸-甘氨酸-甜菜碱。丝氨酸-甘氨酸-甜菜碱由连接丝氨酸的 N-三甲基甘氨酸单元组成。它对 MIA PaCa-2 和 HCT-116 细胞系表现出很强的活性，IC 分别为 8.9 和 15.16 μmol l 。此外，它通过显微镜观察证实了在 MIA PaCa-2 细胞中诱导细胞凋亡。MIA PaCa-2 细胞中凋亡细胞死亡的证据是通过生成细胞内活性氧水平并由于内在途径的激活导致线粒体膜电位丧失来证明的。这项研究描述了基于基因组学（基因组测序、注释和基因比对）的丝氨酸-甘氨酸-甜菜碱的可能生物合成。
从 M. phaseolina 中分离出的新型二肽丝氨酸-甘氨酸-甜菜碱诱导 MIA-Pa-Ca-2 细胞凋亡。
这项研究证实，像丝氨酸-甘氨酸-甜菜碱和酪氨酸-甜菜碱这样的二肽可能是真菌属特有的，因此可用于诊断目的。
