An intramolecular macrocyclase in plant ribosomal peptide biosynthesis.

The biosynthetic dogma of ribosomally synthesized and posttranslationally modified peptides (RiPP) involves enzymatic intermolecular modification of core peptide motifs in precursor peptides. The plant-specific BURP-domain protein family, named after their four founding members, includes autocatalytic peptide cyclases involved in the biosynthesis of side-chain-macrocyclic plant RiPPs. Here we show that AhyBURP, a representative of the founding Unknown Seed Protein-type BURP-domain subfamily, catalyzes intramolecular macrocyclizations of its core peptide during the sequential biosynthesis of monocyclic lyciumin I via glycine-tryptophan crosslinking and bicyclic legumenin via glutamine-tyrosine crosslinking.

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search.

Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra.

A matrigel-free method for culture of pancreatic endocrine-like cells in defined protein-based hydrogels.

The transplantation of pancreatic endocrine islet cells from cadaveric donors is a promising treatment for type 1 diabetes (T1D), which is a chronic autoimmune disease that affects approximately nine million people worldwide. However, the demand for donor islets outstrips supply. This problem could be solved by differentiating stem and progenitor cells to islet cells.

Plant Copper Metalloenzymes As Prospects for New Metabolism Involving Aromatic Compounds.

Copper is an important transition metal cofactor in plant metabolism, which enables diverse biocatalysis in aerobic environments. Multiple classes of plant metalloenzymes evolved and underwent genetic expansions during the evolution of terrestrial plants and, to date, several representatives of these copper enzyme classes have characterized mechanisms. In this review, we give an updated overview of chemistry, structure, mechanism, function and phylogenetic distribution of plant copper metalloenzymes with an emphasis on biosynthesis of aromatic compounds such as phenylpropanoids (lignin, lignan, flavonoids) and cyclic peptides with macrocyclizations via aromatic amino acids.

Discovery and biosynthesis of cyclic plant peptides via autocatalytic cyclases.

Many bioactive plant cyclic peptides form side-chain-derived macrocycles. Lyciumins, cyclic plant peptides with tryptophan macrocyclizations, are ribosomal peptides (RiPPs) originating from repetitive core peptide motifs in precursor peptides with plant-specific BURP (BNM2, USP, RD22 and PG1beta) domains, but the biosynthetic mechanism for their formation has remained unknown. Here, we characterize precursor-peptide BURP domains as copper-dependent autocatalytic peptide cyclases and use a combination of tandem mass spectrometry-based metabolomics and plant genomics to systematically discover five BURP-domain-derived plant RiPP classes, with mono- and bicyclic structures formed via tryptophans and tyrosines, from botanical collections.