Aurachin C

Central-Andean Ecosystems (between 2000 and 6000 m above sea level (masl) are typical arid-to-semiarid environments suffering from the highest total solar and ultraviolet-B radiation on the planet but displaying numerous salt flats and shallow lakes. Andean microbial ecosystems isolated from these environments are of exceptional biodiversity enduring multiple severe conditions. Furthermore, the polyextremophilic nature of the microbes in such ecosystems indicates the potential for biotechnological applications. Within this context, the study undertaken used genome mining, physiological and microscopical characterization to reveal the multiresistant profile of Nesterenkonia sp. Act20, an actinobacterium isolated from the soil surrounding Lake Socompa, Salta, Argentina (3570 masl). Ultravioet-B, desiccation, and copper assays revealed the strain's exceptional resistance to all these conditions. Act20's genome presented coding sequences involving resistance to antibiotics, low temperatures, ultraviolet radiation, arsenic, nutrient-limiting conditions, osmotic stress, low atmospheric-oxygen pressure, heavy-metal stress, and toxic fluoride and chlorite. Act20 can also synthesize proteins and natural products such as an insecticide, bacterial cellulose, ectoine, bacterial hemoglobin, and even antibiotics like colicin V and aurachin C. We also found numerous enzymes for animal- and vegetal-biomass degradation and applications in other industrial processes. The resilience of Act20 and its biotechnologic potential were thoroughly demonstrated in this work.

Cytochrome bd-type oxidases play a crucial role for survival of pathogenic bacteria during infection and proliferation. This role and the fact that there are no homologues in the mitochondrial respiratory chain qualify cytochrome bd as a potential antimicrobial target. However, few bd oxidase selective inhibitors have been described so far. In this report, inhibitory effects of Aurachin C (AurC-type) and new Aurachin D (AurD-type) derivatives on oxygen reductase activity of isolated terminal bd-I, bd-II and bo3 oxidases from Escherichia coli were potentiometrically measured using a Clark-type electrode. We synthesized long- (C10, decyl or longer) and short-chain (C4, butyl to C8, octyl) AurD-type compounds and tested this set of molecules towards their selectivity and potency. We confirmed strong inhibition of all three terminal oxidases for AurC-type compounds, whereas the 4(1H)-quinolone scaffold of AurD-type compounds mainly inhibits bd-type oxidases. We assessed a direct effect of chain length on inhibition activity with highest potency and selectivity observed for heptyl AurD-type derivatives. While Aurachin C and Aurachin D are widely considered as selective inhibitors for terminal oxidases, their structure-activity relationship is incompletely understood. This work fills this gap and illustrates how structural differences of Aurachin derivatives determine inhibitory potency and selectivity for bd-type oxidases of E. coli.

AuaG is flavin-dependent monooxygenase responsible for the conversion of aurachin C to aurachin B, a reaction thought to resemble semipinacol migration of the farnesyl substituent. A study of the substrate tolerance of AuaG reveals that it has the peculiar ability to oxidise short-chain analogues of aurachin D. Unexpectedly, a novel retro-[2,3]-Wittig rearrangement was observed with an isoprenyl substrate analogue, thus leading to the 1,1-dimethylallyl ether. Additionally, we found that saturated-chain analogues of N-oxidised aurachin C were not transformed by the C3→C4 semipinacol reaction, as might have been expected for such substrates. Based on this and the unique retro-[2,3]-Wittig rearrangement, we discuss an alternative biosynthetic route for the conversion of aurachin C to aurachin B.