Genome-based deletion analysis in Aspergillus terreus reveals the acetylaranotin bis-thiomethyltransferase gene

Abstract

Acetylaranotin is an epipolythiodiketopiperazine (ETP) secondary metabolite with a broad range of bioactivities. We demonstrated that ATEG_01465.1 located outside of acetylaranotin gene cluster is responsible for catalyzing the S-methylation of its biosynthetic pathway. Combining the previous characterization of acetylaranotin biosynthetic gene cluster together with the identification of its S-methyltransferase provides a means to obtain second-generation acetylaranotin derivatives previously inaccessible. By permutations of targeted deletions of ATEG_01465.1, acetyltransferase (AtaH), and benzoate hydroxylase (AtaY), three novel acetylaranotin derivatives were produced by Aspergillus terreus.

Non-ribosomal Peptide Synthetase Gene Clusters in the Human Pathogenic Fungus Scedosporium apiospermum

“…For each step, the genes involved as well as their putative function are depicted in pink and blue, respectively. The gene SAPIO_CDS6445, located outside of ETP1828 gene cluster, corresponds to the best hit against gtmA/tmtA and ataS , the major bis-thiomethyltransferase genes responsible for catalyzing the S -methylation step leading to the inactivation of gliotoxin and acetylaranotin compounds, respectively (Dolan et al, 2014; Scharf et al, 2014; Sun et al, 2018). The CDS10214 denotes an unclustered gene coding for a benzoate para-hydroxylase cytochrome P450 potentially responsible for the formation of the dihydrooxepin moiety that converts (i) a diacetate intermediate to aranotin via apoaranotin, (ii) boydin A to bisdethiobis-(methylthio)-deacetylaranotin via bisdethiobis(methylthio)-deacetylapoaranotin, and (iii) boydin B to boydin C. The superscript letters a and b indicate the natural products isolated from S. boydii by Lan et al (2016) and Wu et al (2014), respectively.…”

Epipolythiodioxopiperazine‐Based Natural Products: Building Blocks, Biosynthesis and Biological Activities

“…Similar to gliotoxin, a bis(methylthio)‐variant has been reported [94a] and the corresponding S ‐methyltransferase (AtaS) has been spotted outside the ara cluster. [145] …”