The unique chemistry and biology of the piericidins.
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.
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA, USA.|South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, People's Republic of China.
Xuefeng
X
Zhou
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA, USA.
William
W
Fenical
D039903:Actinobacteria / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D006801:Humans; D007306:Insecticides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000378:metabolism; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D007306:Insecticides; D011725:Pyridines; C100213:piericidin A; D042967:Electron Transport Complex I