Frontispiece: Cacaoidin, First Member of the New Lanthidin RiPP Family

Abstract

Natural Products In their Communication on page 12654, F. J. Ortiz‐López et al. describe a novel glycosylated lantibiotic, cacaoidin, which inaugurates a new RiPP family characterized by the co‐occurrence of lanthionine rings and N‐terminus dimethylation.

Structural Analysis of Class I Lanthipeptides from Pedobacter lusitanus NL19 Reveals an Unusual Ring Pattern

“…How this enzymatic control over cyclization is achieved without the canonical Zn 2+ ligands will be an interesting topic for future mechanistic studies. We note that nearly all of the LanC cyclases associated with PedA15-like precursors lack the canonical zinc-binding ligands (Figure S17), but they all contain the His that is believed to protonate the enolate. , The absence of a Zn 2+ site in lanthipeptide cyclases is increasingly reported for other classes of lanthipeptides, but no information about the molecular mechanisms used by these cyclases is currently available. , …”

“…61,63 The absence of a Zn 2+ site in lanthipeptide cyclases is increasingly reported for other classes of lanthipeptides, but no information about the molecular mechanisms used by these cyclases is currently available. 7,64 ■ CONCLUSION Herein, we report the heterologous expression and structural characterization of two lanthipeptides from P. lusitanus NL19. Our data indicate that expression of the ped15 biosynthetic machinery in E. coli produces modified peptides only if the tRNA Glu and GluRS from the native producer are coexpressed.…”

“…One of the most extensively studied classes of RiPPs is the lanthipeptides, which are characterized by the presence of lanthionine (Lan) and methyllanthionine (MeLan) residues that result in complex polycyclic peptide structures that may be further tailored with additional post-translational modifications. , The (Me)­Lan cross-links can be installed by one of five classes of lanthipeptide synthase systems (classes I–V), which first dehydrate target Ser and Thr residues in the core peptide to generate dehydroalanine (Dha) and dehydrobutyrine (Dhb). ,− Cysteine residues located in the core peptide then react with these dehydrated residues via intramolecular Michael-type addition to form the thioether rings.…”

Lanthipeptides from the Same Core Sequence: Characterization of a Class II Lanthipeptide Synthetase from Microcystis aeruginosa NIES-88

“…The final product is formed upon removal of the unmodified leader by a peptidase . To date, lanthipeptides are classified into five classes based on the PTM enzymes that install the characteristic Lan/MeLan motifs (Figure A). − Generally, Ser and Thr residues in the core are dehydrated to form dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues through a phosphorylation or glutamylation mechanism, followed by a conjugate addition of a Cys free thiolate, leading to the formation of Lan/MeLan motifs . In most cases, lanthipeptide PTM enzymes recognize specific leader sequences but are promiscuous with the core sequences.…”

Deciphering the Biosynthesis of Novel Class I Lanthipeptides from Marine Pseudoalteromonas Reveals a Dehydratase PsfB with Dethiolation Activity

“…Recently, the class V lanthipeptide biosynthetic pathway was identified and characterized. A kinase/lyase pair (LanK/LanY) and a class I cyclase LanC were found to be responsible for the dehydration and cyclization reactions. ,− Apart from the difference between the biosynthetic enzymes, five classes of lanthipeptides can also be distinguished based on the biosynthetic machinery utilized by these enzymes. Class I LanB dehydratase uses glutamyl-tRNA Glu to activate the hydroxyl side chains of Ser/Thr residues followed by glutamate elimination , (Figure A).…”