Actinobacteria-Derived peptide antibiotics since 2000

Abstract

Members of the Actinobacteria, including Streptomyces spp., Kutzneria sp. Actinoplanes spp., Actinomycete sp., Nocardia sp., Brevibacteriumsp.,Actinomadura spp., Micromonospora sp., Amycolatopsis spp., Nonomuraea spp., Nocardiopsis spp., Marinactinospora sp., Rhodococcus sp., Lentzea sp., Actinokineospora sp., Planomonospora sp., Streptomonospora sp., and Microbacterium sp., are an important source of structurally diverse classes of short peptides of ∼30 residues or fewer that will likely play an important role in new antibiotic development and discovery. Additionally, many have unique structures that make them recalcitrant to traditional modes of drug resistance via novel mechanisms, and these are ideal therapeutic tools and potential alternatives to current antibiotics. The need for novel antibiotic is urgent, and this review summarizes 199 Actinobacteria compounds published since 2000, including 35 cyclic lipopeptides containing piperazic or pipecolic acids, eight aromatic peptides, five glycopeptides, 21 bicyclic peptides, 44 other cyclic lipopeptides, five linear lipopeptides, six 2,5-diketopiperazines, one dimeric peptide, four nucleosidyl peptides, two thioamide-containing peptides, 25 thiopeptides, nine lasso peptides, and 34 typical cyclic peptides. The current and potential therapeutic applications of these peptides, including their structure, antituberculotic, antibacterial, antifungal, antiviral, anti-brugia, anti-plasmodial, and anti-trypanosomal activities, are discussed.

Keywords: Actinobacteria; Antibiotic activity; Lasso peptide; Lipopeptide; Structural sequence; Thiopeptide.