Aspergillus fumigatus Mitochondrial Acetyl Coenzyme A Acetyltransferase as an Antifungal Target
Yuanwei Zhang, Wenfan Wei, Jialu Fan, Cheng Jin, Ling Lü, Wenxia Fang
Abstract
A growing number of people worldwide are suffering from invasive aspergillosis caused by the human opportunistic fungal pathogen A. fumigatus . Current therapeutic options rely on a limited repertoire of antifungals. Ergosterol is an essential component of the fungal cell membrane as well as a target of current antifungals. Approximately 20 enzymes are involved in ergosterol biosynthesis, of which acetyl-CoA acetyltransferase (ACAT) is the first enzyme. Two ACATs in A. fumigatus are Af Erg10A and Af Erg10B. However, the biological function of Af Erg10A is yet to be investigated. In this study, we showed that Af Erg10A is localized in the mitochondria and is essential for A. fumigatus survival and morphological development. In combination with structural studies, we validated Af Erg10A as a potential drug target that will facilitate the development of novel antifungals and improve the efficiency of existing drugs.