Biosynthesis of a Novel Diketopiperazine Aspkyncin Incorporating a Kynurenine Unit from Aspergillus aculeatus
Year: 2025
Type: article
Abstract: The simplest cyclo-peptides, also known as diketopiperazines (DKPs), are widespread in nature. The growing interest in these simplest cyclo-peptides is driven by their significant potential for therapeutic applications. In this study, we identified a biosynthetic gene cluster from Aspergillus aculeatus CRI323-04 through genome mining and heterologous expression in Aspergillus nidulans. The two core genes, aacA and aacB, within the gene cluster were characterized for their role in the biossoynthesis of aspkyncin, a novel DKP compound that incorporates a l-kynurenine (l-Kyn) unit. Furthermore, we successfully reconstituted the activities of the minimal bimodular non-ribosomal peptide synthetase (NRPS) AacA and the methyltransferase AacB both in vivo and in vitro. Our findings demonstrate that AacA catalyzes the condensation and cyclization of two non-proteinogenic amino acids, l-Kyn and N-methyl-l-alanine, to produce aspkyncin without the involvement of any release domain. Notably, the N-methyl-l-alanine is generated by a specialized l-alanine N-methyltransferase AacB prior to NRP assembly. This study reveals an unconventional pathway for the biosynthesis of fungal DKPs.
Source: Journal of Fungi
DOI: 10.3390/jof11030171
Authors: Dekun Kong, Xin Wang, Li Liu
Institutions: Southwest University, Chongqing Medical University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W4407766759