As a leading company in the field of antifungal drug discovery, Creative Biolabs has successfully developed a full range of methods for potential target identification and validation. Based on the advanced technology platform and experienced scientists, now we are capable of providing electron transport target exploiting service to accelerate the development of global customers’ programs.

Introduction of Electron Transport Chain

The electron transport chain (ETC) is composed of 5 complexes, of which three large protein complexes namely NADH: ubiquinone oxidoreductase (Complex I), ubiquinol: cytochrome c oxidoreductase (Complex III) and cytochrome c oxidase (Complex IV) provide the proton gradients that result in ATP synthesis by CV. Of these, CI is the largest in molecular weight, generates about one-half of all mtATP. CI is comprised of a variable number of subunit proteins that are assembled by accessory proteins. In each complex electron transport is coupled to proton translocation, with the resultant protonmotive force (pmf) being used for ATP synthesis and transport of metabolites. Each complex has characteristic inhibitors, e.g. rotenone and piericidin (Complex I), antimycin and myxothiazol (Complex III) and cyanide (Complex IV). Electrons from succinate reach ubiquinone without coupled proton transfer (Complex II).

Electron transport chain and its interactors. Fig.1 Electron transport chain and its interactors. (Vos, 2015)

Electron Transport Chain as Potential Antifungal Target

Studies have shown that if there is CI dysfunction, then a concomitant increase in superoxide occurs that is detrimental to cells. It is quite apparent that if cells are starved of mitochondrial ATP, cellular synthesis diminishes and events have triggered that result in cell death. In other words, CI deficient mutants accumulate mitochondrial ROS, lose chronological aging, and undergo apoptosis. Under this condition, therapies to target the mitochondria electron transport chain of fungal pathogens would be useful. Until now, 2 subunits (Nuo1p and Nuo2p) have been identified which are either solely fungal-specific or limited to fungi, green algae, and plants. They are both NADH: Ubiquinone Oxidoreductases and can be exploited as antifungal drug targets.

In the past years, we have provided numerous antifungal target discovery services for worldwide customers. We are happy to offer high-quality target identification and validation services through various methods, such as WGS, computer-aided target identification, and validation, gene expression profiling, etc. Except for electron transport chain, we also provide other potential cellular function-related targets exploiting services for antifungal drug discovery, which including but not limited to:

Creative Biolabs is committed to promoting the development of global customers’ programs. To learn more information about our antifungal drug discovery services, please feel free to contact us.

Reference

  1. Vos, M.; et.al. Stimulation of electron transport as potential novel therapy in Parkinson's disease with mitochondrial dysfunction. 2015, 275-279.

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