Non-lipopeptide fungi-derived peptide antibiotics developed since 2000

Abstract

The 2,5-diketopiperazines (DKPs) are the smallest cyclopeptides and their basic structure includes a six-membered piperazine nucleus. Typical peptides lack a special functional group in the oligopeptide nucleus. Both are produced by at least 35 representative genera of fungi, and possess huge potential as pharmaceutical drugs and biocontrol agents. To date, only cyclosporin A has been developed into a commercial product. This review summarises 186 fungi-derived compounds reported since 2000. Antibiotic (antibacterial, antifungal, synergistic antifungal, antiviral, antimycobacterial, antimalarial, antileishmanial, insecticidal, antitrypanosomal, nematicidal and antimicroalgal) activities are discussed for 107 of them, including 66 DKPs (14 epipolythiodioxopiperazines, 20 polysulphide bridgefree thiodiketopiperazines, and 32 sulphur-free prenylated indole DKPs), 15 highly N-methylated, and 26 non-highly N-methylated typical peptides. Structureactivity relationships, mechanisms of action, and research methods are covered in detail. Additionally, biosynthases of tardioxopiperazines and neoechinulins are highlighted. These compounds have attracted considerable interest within the pharmaceutical and agrochemical industries.

Structures and Biological Activities of Diketopiperazines from Marine Organisms: A Review

“…Peniciadametizine A ( 150 ) and B ( 151 ) were isolated from the fungus Penicillium adametzioides AS-53 collected from an unidentified sponge in Hainan Island of China. Compound 150 had a unique spiro[furan-2,7’-pyrazino[1,2-b][ 1 , 2 ]oxazine] skeleton, which was found from a natural source for the first time and compound 151 was the highly oxygenated analogue of 150 . In a dose of 100 μg/mL, compounds 150 and 151 could kill Artemia salina with the lethal ratio of 45.5 and 62.4%, respectively.…”

“…The 2,5-diketopiperazines (DKPs), the smallest cyclic dipeptides from the double condensations of two α -amino acids, are abundant in nature and possess a six-membered piperazine rigid backbone [ 1 , 2 ]. The formation of two peptide bonds in DKPs are catalyzed by two major enzymes, the nonribosomal peptide synthetases (NRPSs, >100 kDa) and cyclodipeptide synthases (CDPSs, 30 kDa) [ 3 ].…”

Natural Products from Endophytic Fungi Associated with Rubiaceae Species

“…Fungi secondary metabolites are categorized in chemical classes: polyketides [ 56 , 57 , 58 , 59 ], non-ribosomal peptides [ 57 , 59 , 60 , 61 , 62 ], ribosomal peptides [ 62 , 63 , 64 ], terpenes [ 65 , 66 , 67 ], and hybrid metabolites [ 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. These chemical classes are synthesized by specialized class-defining (backbone) enzymes such as polyketides synthases (PKSs), non-ribosomal peptide synthetases (NRPSs), terpene cyclases (TCs), and dimethylallyl tryptophan synthases (DMATSs), respectively.…”

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

“…All these features make CDPs an attractive choice as biocompatible, green, functionalizable, and cheap building blocks for smart materials with a wide scope of applications from industry to medicine. The basic design is very simple: two amino acids bound together in a cyclic structure with a defined stereochemistry (i.e., LL, LD/DL, or DD) and the possibility to further derivatize the side chains [ 42 , 43 , 44 , 45 , 46 ] of selected amino acids [ 47 , 48 , 49 , 50 ], as widely applied in nature [ 51 , 52 , 53 , 54 , 55 , 56 ].…”

“…Thus, materials obtained by these molecules could be versatile [ 41 ]. There is growing interest in CDPs, and recent reviews exist that discuss their bioactivity [ 58 , 61 , 62 ], supramolecular organization [ 31 , 40 ], and use as scaffolds for drug discovery [ 52 , 63 , 64 , 65 , 66 ].…”