Enzymatic Generation of Thioaldehyde Motifs by Flavin-Dependent Cysteine Decarboxylases for Peptide Bioconjugation and Macrocyclization

Xia, Yinzheng; Yi, Yuchen; Shi, Ying; Long, Tengfang; Wang, Huan

doi:10.1021/acs.orglett.3c02184

Cited by 4 publications

(1 citation statement)

References 29 publications

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“…[8,9] Additionally, the enethiol motif can spontaneously isomerize to a thioaldehyde, a highly electrophilic species for peptide bioconjugation and macrocyclization. [14]…”

Section: Enzymatic Formation Of An Enethiol Intermediatementioning

confidence: 99%

Enzymatic Formation of an Aminovinyl Cysteine Residue in Ribosomal Peptide Natural Products

Cheng,

Xue,

Duan

et al. 2024

ChemPlusChem

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The carboxyl‐terminal (C‐terminal) S‐[(Z)‐2‐aminovinyl]‐cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post‐translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD‐like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species. The collaborative actions of LanD‐like proteins with diverse enzymes involved in dehydration, dethiolation or cyclization lead to the construction of structurally distinct peptide natural products with analogous C‐terminal macrocyclic moieties. This concept summarizes existing knowledge regarding biosynthetic pathways of AviCys analogs to emphasize the diversity of biosynthetic mechanisms that paves the way for future genome mining explorations into diverse peptide natural products.

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“…[8,9] Additionally, the enethiol motif can spontaneously isomerize to a thioaldehyde, a highly electrophilic species for peptide bioconjugation and macrocyclization. [14]…”

Section: Enzymatic Formation Of An Enethiol Intermediatementioning

confidence: 99%