A precursor peptide is typically composed of a leader and core peptide (Fig. In many instances, a set of accessory genes that encode transporters and/or tailoring enzymes are co-localized with the essential genes within the BGC. Two prominent examples are the lanthipeptide nisin that is used as a food preservative to suppress food-borne bacterial growth (Gharsallaoui et al., 2016) and the conapeptide ziconotide that is an FDA approved analgesic under the trade name of Prialt (McGivern, 2007 Schmidtko et al., 2010).īiosynthetically, the minimal essential architecture of a RiPP biosynthetic gene cluster (BGC) comprises genes that encode for the precursor peptide and core enzymes that catalyze post-translational modifications (Fig. RiPPs have also been realized for their diverse bioactivities and potential commercial uses (Cao et al., 2021 Ongpipattanakul et al., 2022). Apart from their chemical and functional diversity, RiPPs have received significant scientific attention due to substrate tolerance, susceptibility to pathway engineering (Wu & van der Donk, 2021), and thermal and proteolytic stability (Montalbán-López et al., 2021). RiPPs originate from the ribosome and are present in prokaryotes (Arnison et al., 2013), eukaryotes (Luo & Dong, 2019), and archaea (Besse et al., 2015). To date, there are >40 classes of RiPPs (Hubrich et al., 2022 Montalbán-López et al., 2021 Ortiz-López et al., 2020 Russell et al., 2021 Wang et al., 2022). The ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly growing class of secondary metabolites that are recognized for their structural and functional diversity (Arnison et al., 2013 Montalbán-López et al., 2021). Secondary metabolites are a valuable source of bioactive compounds with broad applications, such as in medicine (Newman & Cragg, 2020) and agriculture (Yan et al., 2018). With the continuous improvement of the bioinformatic tools for RiPP prediction and advancement in synthetic biology techniques, it is expected that further cytochrome P450-mediated RiPP biosynthetic pathways will be discovered. Formation of some RiPPs is catalyzed by more than one P450, enabling structural diversity. While the number of characterized P450s involved in RiPP biosyntheses is relatively small, they catalyze various enzymatic reactions such as C–C or C–N bond formation. Previous studies have revealed a wealth of P450s distributed across all domains of life. In this review, we focus our discussion on P450 involved in RiPP pathways and the unique chemical transformations they mediate. Of these enzymes, cytochromes P450 (P450s) are a superfamily of heme-thiolate proteins involved in many metabolic pathways, including RiPP biosyntheses. RiPPs derive from the cleavage of ribosomally synthesized proteins and additional modifications, catalyzed by various enzymes to alter the peptide backbone or side chains.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large class of secondary metabolites that have garnered scientific attention due to their complex scaffolds with potential roles in medicine, agriculture, and chemical ecology.
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