Cyclodipeptides: An Overview of Their Biosynthesis and Biological Activity

Abstract

Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters. In this review, we provide a comprehensive summary of CDP biosynthetic pathways and modifying enzymes. We also discuss the biological properties of some known CDPs and their possible applications in metabolic engineering.

Cyclic Peptides in Neurological Disorders: The Case of Cyclo(His-Pro)

“…CDPs, also known as 2,5-diketopiperazines, are a family of small and biologically active molecules, mostly acting as QS effectors, that contain a family-defining CDP core/scaffold structure (Fig. 1), and are produced by proteobacterial species as well as by humans (Bellezza et al, 2014a,b;Borthwick, 2012;Cornacchia et al, 2012;Minelli et al, 2008;Mishra et al, 2017;Prasad, 1995). CDPs are a class of cyclic organic compounds in which the two nitrogen atoms of a piperazine 6-membered ring form amide linkages.…”

“…CDPs exhibit better biological activity than their linear counterparts due to their higher stability, protease resistance, and conformational rigidity, all factors that increase their ability to specifically interact with biological targets (Liskamp et al, 2011;Menegatti et al, 2013). They constitute a large class of secondary metabolites produced by bacteria, fungi, plants, and animals (Borthwick, 2012;Giessen and Marahiel, 2014;Huang et al, 2010;Mishra et al, 2017;Prasad, 1995). Indeed, approximately 90% of CDP producers are bacterial (Giessen and Marahiel, 2014).…”

“…(PAI-1), enabling intervention in cardiovascular disease and blood clotting functions (Einholm et al, 2003), was the first discovered biological action of CDPs, later followed by the discovery of antibacterial (Rhee, 2004), antitumor (Nicholson et al, 2006), antifungal, and antiviral activities (Kwak et al, 2013;Kwak et al, 2014;Mishra et al, 2017). Korean fermented vegetable kimchi is a rich source of Pro-based CDPs that have activities against multidrug resistant bacteria (Liu et al, 2017), and cyclo(L-Val-L-Pro) and cyclo(L-Phe-L-Pro), produced by vegetables fermented with Lactobacillus plantarum LBP-K10, can inhibit the growth of Candida albicans (Kwak et al, 2014).…”

Bioactivities and molecular networking-based elucidation of metabolites of potent actinobacterial strains isolated from the Unkeshwar geothermal springs in India

“…Cyclic peptides are of signicant importance due to their medical properties, especially those containing isodityrosine, as they have diverse biological activities, including antimicrobial, antiviral and antitumor activities. 42 However, these compounds have rarely been isolated from Actinobacteria. In our study, the extract of Micromonospora sp.…”

Ionic Liquid Mediated Ugi/SN2 Cyclization: Synthesis of 1,2,3-Triazole Containing Novel 2,5-Diketopiperazines

“…Herein we report a Ugi 4CR with 4-((1-((tetrahydrofuran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde Figure 1 as aldehyde component that contains triazole moiety. Triazoles are an important class of heterocycles in the context of pharmacological properties, such as antifungal, [7] antibacterial [8,9], anticancer [10], and antimicrobial [11]. In our research investigation group, Erick Cuevas et al have developed a functionalization and incorporation of triazole moiety to aromatic aldehydes.…”