Isolation and Physiological Activities of Piericidin A, A Natural Insecticide Produced by Streptomyces

The myxalamids, new antibiotics from Myxococcus xanthus (Myxobacterales) I. production, physico-chemical and biological properties, and mechanism of action.

“…6.5.3) of beef heart submitochondrial particles. The high toxicity of myxalamid B for mammalian systems is thus understandable; it is in the same range or even higher than that of the piericidins16, 17) In contrast to the respiration inhibitor myxothiazol2), which acts at the cytochrome bc1segment19), myxalamid B had a relatively narrow antibiotic spectrum. Only some molds, few yeasts, and a number of bacteria, mainly Gram-positive ones, were inhibited.…”

The unique chemistry and biology of the piericidins

“…Boger and co-workers reported the first total synthesis of piericidin A (1) and B1 (3) in 2005 in an early paper, 40 and then provided full details in the next year. 39 Shortly following Boger's preliminary disclosure, Keaton and Phillips 41 reported a complementary total synthesis of 7-demethylpiericidin A1 (30), a natural product closely related to piericidin A (1).…”

“…Piericidins were first discovered because of their insecticidal activity, 3,62 and mechanistic studies indicated that complex I was the molecular target of piericidins. 63 Besides its well-known redox role in the electron transport chain, complex I is also considered to be one of the main production sites of reactive oxygen species (ROS).…”

“…The original reports included details of its isolation, physiological activity, functional groups and a partial structure. [3][4][5] The structure of piericidin A was originally proposed in 1965 as 1a (Figure 1) on the basis of extensive degradation studies and analysis of the 1 H NMR data. 6 Piericidin A resembles coenzyme Q in its overall structure containing a pyridine ring with two adjacent methoxy groups, rather than the identically substituted p-benzoquinone functionality.…”

“…Piericidin B (3, also named piericidin B1 in some references) was also originally observed in the cultivation of Streptomyces mobaraensis in 1963. 3 Piericidin B was assigned as the C-10 methoxy analog of A, apparently produced during fermentation and work-up. 9 Sometime later, Takahashi reported that 14 new piericidins could be extracted from the cultured mycelium of Streptomyces pactum.…”