Cleaning the Cellular Factory–Deletion of McrA in Aspergillus oryzae NSAR1 and the Generation of a Novel Kojic Acid Deficient Strain for Cleaner Heterologous Production of Secondary Metabolites

The use of filamentous fungi as cellular factories, where natural product pathways can be refactored and expressed in a host strain, continues to aid the field discovery. Much work has been done develop strains which are genetically tractable, for there multiple selectable markers controllable expression systems. To fully exploit these strains, it is beneficial understand their metabolic capabilities, such knowledge rule out metabolites from analysis transgenic lines highlight any potential interplay between endogenous exogenous pathways. Additionally, once identified, deletion secondary metabolite simplify detection purification heterologous compounds. this end, production Aspergillus oryzae strain NSAR1 investigated via newly discovered negative regulator metabolism, mcrA (multicluster A). In all ascomycetes previously studied led an increase production. Surprisingly, only detectable phenotypic change was doubling yields kojic acid, with no novel produced. This supports previous claim that repressed A. demonstrates repression not McrA-mediated. Strain then modified by employing CRISPR-Cas9 technology disrupt generating NSAR?K, combines various traits uniquely clean background.