The unique chemistry and biology of the piericidins

Abstract

The piericidin family of microbial metabolites features a 4-pyridinol core linked with a methylated polyketide side chain. Piericidins are exclusively produced by actinomycetes, especially members of the genus Streptomyces. The close structural similarity with coenzyme Q renders the piericidins important NADH-ubiquinone oxidoreductase (complex I) inhibitors in the mitochondrial electron transport chain. Because of the significant activities of the piericidins, which include insecticidal, antimicrobial and antitumor effects, total syntheses of the piericidins were developed using various synthetic strategies. The biosynthetic origin of this class has also been the subject of investigation. This review covers the isolation and structure determination of the natural piericidins, their chemical modification, the total syntheses of natural and unnatural analogs, their biosynthesis, and reported biological activities together with structure-activity relationships. Given the fundamental biology of this class of metabolites, the piericidin family will likely continue to attract attention as biological probes of important biosynthetic processes.

Marine Actinobacteria as a source of compounds for phytopathogen control: An integrative metabolic-profiling / bioactivity and taxonomical approach

“…m/z 227.2 tentatively identified as Nikkomycin D from Streptomyces tendae , and m/z 446.6 tentatively identified as Piericydin-C2 compounds with antibacterial and anthelmintic activity isolated from Streptomyces piericidicus and S . pactum [ 91 , 92 ]; δ-lactones (e.g. m/z 245.3 tentatively identified as Graefe’s Factor I, inducer of anthracycline production isolated from Streptomyces viridochromogenes ) [ 93 , 94 ]; fatty acid derivatives (e.g.…”

New Insights into the Biosynthesis Pathway of Polyketide Alkaloid Argimycins P in Streptomyces argillaceus

“…Most of these compounds are peptides (ribosomal and non-ribosomal synthesized), polyketides or terpenes. Particularly, several piperidine-containing alkaloids of polyketide origin have been isolated from actinomycetes, such as coelimycin P ( Gómez-Escribano et al, 2012 ), cyclizidine ( Freer et al, 1982 ), iromycins ( Surup et al, 2007 ), latumcidin (also known as abikoviromycin; Seto et al, 1973 ), piericidins ( Zhou and Fenical, 2016 ), strepchazolins ( Yang et al, 2017 ), streptazolins ( Mayer and Thiericke, 1993 ; Puder et al, 2001 ), streptazones A–D ( Puder et al, 2000 ), streptazone E ( Liu et al, 2013 ), or streptopyridines ( Groenhagen et al, 2014 ). These compounds show a range of activities such as antimicrobial, antiviral, cytotoxic, decreasing blood pressure and cholesterol biosynthesis, or analgesic ( Umezawa et al, 1951 ; Terashima et al, 1970 ; Grabley et al, 1991 ; Puder et al, 2001 ).…”

New Cytotoxic Cyclic Peptide from the Marine Sponge-Associated Nocardiopsis sp. UR67

“…UR67. The dereplication study of the metabolites ( Figure 2 , Table 1 ) against the Dictionary of Natural Products (DNP) database, AntiMarin, and METLIN databases led to the characterization of the following natural products: cytotoxic peptide lucentamycin C [ 28 ], immunosuppressant kanglemycin M [ 29 ], 8-hydroxy-3-methoxy-1-methyl-anthraquinone-2-carboxylic acid [ 30 ], antimicrobial, antitumor and insecticidal piericidin-C3 [ 31 ], sotetracenone-type antitumor atramycin B [ 32 ], piericidin group antibiotic IT-143-B [ 33 ], antibiotic lankacyclinol-A [ 34 ], antifungal polyketide ansatrienin A [ 35 ], actinoramide B [ 36 ] and, finally, a potent apoptosis inducer polyoxypeptin A [ 37 ].…”