Discovery and biosynthesis of cyclic plant peptides via autocatalytic cyclases

Abstract

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Plant Copper Metalloenzymes As Prospects for New Metabolism Involving Aromatic Compounds

“…The BURP domain was recently characterized in a precursor peptide for lyciumins from Chinese wolfberry (Lycium barbarum) by transient expression of the corresponding BURP domain precursor peptide LbaLycA in Nicotiana benthamiana and subsequent detection of lyciumin chemotypes in transgenic tobacco leaf tissue, which established this domain being connected to RiPP biosynthesis in plants (Kersten and Weng, 2018). Subsequently, several BURP domains associated with plant RiPPs could be reconstituted in vitro in the presence of Cu(II), proving the catalytic role of BURP domains (Chigumba et al, 2021). Based on these studies, two general types of BURP domain precursor peptides can be distinguished.…”

“…Metabolic reactions catalyzed by these enzymes are diverse oxidative transformations that use dioxygen as a general oxidant ( Figure 1 ; Solomon et al, 2014 ). In addition, we review a recent addition to plant copper enzymes in BURP domain peptide cyclases ( Chigumba et al, 2021 ), which have yet to be characterized in their use of dioxygen. Laccases catalyze one-electron oxidations of monophenolic substrates in order to generate phenoxy radicals, which subsequently react with each other to form neolignans, such as (+)-pinoresinol via stereoselective guidance by non-catalytic dirigent proteins ( Davin et al, 1997 ), or lignin and urushiol polymers via oxidative coupling ( Barros et al, 2015 ; Figure 1A ).…”

“…These enzymes reduce oxidative stress from reactive oxygen species and generate oxygen and hydrogen peroxide for lignin biosynthetic laccases and class III peroxidases, respectively ( Barros et al, 2015 ). Finally, BURP domain peptide cyclases catalyze the formation of chemically diverse crosslinks between tyrosine and tryptophan amino acid side chains and unactivated carbons in other amino acids ( Figure 1H ; Chigumba et al, 2021 ). Characterized BURP domain peptide cyclases are autocatalytic enzymes, which are involved in the biosynthesis of plant ribosomally-encoded and posttranslationally-modified peptides (RiPPs) with side-chain-derived macrocyclizations ( Chigumba et al, 2021 ).…”

“…Finally, BURP domain peptide cyclases catalyze the formation of chemically diverse crosslinks between tyrosine and tryptophan amino acid side chains and unactivated carbons in other amino acids ( Figure 1H ; Chigumba et al, 2021 ). Characterized BURP domain peptide cyclases are autocatalytic enzymes, which are involved in the biosynthesis of plant ribosomally-encoded and posttranslationally-modified peptides (RiPPs) with side-chain-derived macrocyclizations ( Chigumba et al, 2021 ). BURP-domain-derived RiPPs are mono- or bicyclic peptides with C(sp 3 )-C(sp 2 )-, C(sp 3 )-O- and C(sp 3 )-N-crosslinks.…”

“…Copper is an essential trace metal for plants that is required for control of the cellular redox state and electron transport reactions in oxidative phosphorylation and photosynthesis. It is also an important cofactor for metabolic reactions in lignin biosynthesis during cell wall formation and in biosynthesis of alkaloids, flavonoids, lignans and cyclic peptides ( Barros et al, 2015 ; Chigumba et al, 2021 ). Copper is a redox-active transition metal and generally exists in two oxidation states, Cu(I) and Cu(II), under plant physiological conditions.…”