Linoleate diol synthase related enzymes of the human pathogens Histoplasma capsulatum and Blastomyces dermatitidis

Ernst H Oliw

doi:10.1016/j.abb.2020.108669

Abstract

Histoplasma capsulatum is an ascomyceteous fungus and a human lung pathogen, which is present in river valleys of the Americas and other continents. H. capsulatum and two related human pathogens, Blasmomyces dermatitidis and Paracoccidioides brasiliensis, belongs to the Ajellomycetaceae family. The genomes of all three species code for three homologous and tentative enzymes of the linoleate diol synthase (LDS) family of fusion enzymes with dioxygenase (DOX) and cytochrome P450 domains. One group aligned closely with 8R-DOX-5,8-LDS of Aspergilli, which oxidizes linoleic acid to 5S,8R-dihydroxylinoleic acid; this group was not further investigated. The second group aligned with 10R-DOX-epoxy alcohol synthase (EAS) of plant pathogens. Expression of this enzyme from B. dermatitidis revealed only 10R-DOX activities, i.e., oxidation of linoleic acid to 10R-hydroperoxy-8E,12Z-octadecadienoic acid. The third group aligned in a separate entity. Expression of these enzymes of H. capsulatum and B. dermatitidis revealed no DOX activities, but both enzymes transformed 13S-hydroperoxy-9Z,11E-octadecadienoic acid efficiently to 12(13S)epoxy-11-hydroperoxy-9Z-octadecenoic acid. Other 13-hydroperoxides of linoleic and α-linolenic acids were transformed with less efficiency and the 9-hydroperoxides of linoleic acid were not transformed. In conclusion, a novel EAS has been found in H. capsulatum and B. dermititidis with 13S-hydroperoxy-9Z,11E-octadecadienoic acid as the likely physiological substrate.

Highlights

Histoplasma capsulatum is an ascomyceteous fungus, which is found in river valleys worldwide [1]
We report that the enzymes from H. capsulatum and B. dermatitidis of this group lacked DOX activities, but they transformed 13S-hydroperoxylinoleic efficiently to 12(13S)epoxy11-hydroxy-9Z-octadecenoic acid
Homologues of 8R-DOX-5,8-linoleate diol synthase (LDS) Amino acid sequence alignments showed that three putative DOX

Summary

Introduction

Histoplasma capsulatum is an ascomyceteous fungus, which is found in river valleys worldwide [1]. Inhalation of spores of H. capsulatum can cause histoplasmosis, a lung disease [2]. Histoplasmosis may cause se vere symptoms in immunocompromized patients, but it is not a conta gious disease. All three belong to the Ajellomycetaceae family and they can produce lung infections with spread to internal organs [5]. These fungi are thermally dimorphic, i.e., they can switch between growth as filamentous fungi at 25 ◦C and budding yeasts at 37 ◦C [1,2,3,4,5]

Objectives

Results

Conclusion