Tubulin-Based Microtentacles Aid in Heterotypic Clustering of Neutrophil-Differentiated HL-60 Cells and Breast Tumor Cells.

Circulating tumor cells (CTCs) travel through the vasculature to seed secondary sites and serve as direct precursors of metastatic outgrowth for many solid tumors. Heterotypic cell clusters form between CTCs and white blood cells (WBCs) and recent studies report that a majority of these WBCs are neutrophils in patient and mouse models. The lab discovered that CTCs produce tubulin-based protrusions, microtentacles (McTNs), which promote reattachment, retention in distant sites during metastasis and formation of tumor cell clusters.

The biotoxin BMAA promotes mesenchymal transition in neuroblastoma cells.

Mesenchymal-like cancer cells are an indicator of malignant tumors as they exhibit tumorigenic properties including downregulation of differentiation markers, and increased colony-forming potential, motility, and chemoresistance. We have previously demonstrated that the cyanobacterial biotoxin beta-methylamino-L-alanine (BMAA) is capable of influencing neural cell differentiation state through mechanisms involving the Wnt signaling pathway, suggesting the possibility that BMAA may play a role in influencing other Wnt related differentiation processes including mesenchymal transition. In this study we present evidence characterizing the effects of BMAA on mesenchymal transition in a human neuroblastoma cell line and provide support for the hypothesis that the biotoxin can promote this process in these cells by altering differentiation state, inducing changes in gene expression, and changing cellular function in manners consistent with cellular mesenchymal transition.

The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site.

The Psilocybe cubensis SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM and PsiM, were generated to further examine the role of Asn247 for mono- and dimethylation in PsiM.

Methyl transfer in psilocybin biosynthesis.

Psilocybin, the natural hallucinogen produced by Psilocybe ("magic") mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.

Biosynthetic incorporation of fluorinated amino acids into the nonribosomal peptide gramicidin S.

Fluorine is a key element in medicinal chemistry, as it can significantly enhance the pharmacological properties of drugs. In this study, we aimed to biosynthetically produce fluorinated analogues of the antimicrobial cyclic decapeptide gramicidin S (GS). However, our results show that the A-domain of the NRPS module GrsA rejects 4-fluorinated analogues of its native substrate Phe due to an interrupted T-shaped aromatic interaction in the binding pocket.