Identification of the Neoaspergillic Acid Biosynthesis Gene Cluster by Establishing an In Vitro CRISPR-Ribonucleoprotein Genetic System in Aspergillus melleus.
ACS Omega
; 8(19): 16713-16721, 2023 May 16.
Article
em En
| MEDLINE
| ID: mdl-37214671
ABSTRACT
Filamentous fungi are an essential source of bioactive mycotoxins. Recent efforts have focused on developing antifungal agents that are effective against invasive yeasts, such as Candida spp. By screening fungal strains isolated from regions surrounding the Chernobyl nuclear power plant disaster for antifungal activity against Candida albicans, we found that Aspergillus melleus IMV 01140 produced compounds that inhibited the growth of the yeast. The active compound produced by A. melleus was isolated and found to be neoaspergillic acid, a compound that is closely related to aspergillic acid. While aspergillic acid and its derivatives have been characterized and were found to have antibacterial and antifungal properties, neoaspergillic acid has been much less studied. Even though neoaspergillic acid and related compounds were found to have antibacterial and antitumoral effects, further investigation into this group of compounds is limited by challenges associated with large-scale production, isolation, and purification. The production of neoaspergillic acid has been shown to require co-cultivation methods or special growth conditions. In this work, neoaspergillic acid and related compounds were found to be produced by A. melleus under laboratory growth conditions. The biosynthetic gene cluster of neoaspergillic acid was predicted using the aspergillic acid gene cluster as a model. The biosynthetic pathway for neoaspergillic acid was then confirmed by establishing an in vitro CRISPR-ribonucleoprotein system to individually delete genes within the cluster. A negative transcriptional factor, mcrA, was also eliminated to further improve the production of neoaspergillic acid and the related compounds for future studies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
ACS Omega
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos