Abstract
Fungi are a prospective resource of bioactive compounds, but conventional methods of drug discovery are not effective enough to fully explore their metabolic potential. This study aimed to develop an easily attainable method to elicit the metabolic potential of fungi using Aspergillus nidulans laeA as a transcription regulation tool. In this study, functional analysis of Aspergillus nidulans laeA (AnLaeA) and Aspergillus sp. Z5 laeA (Az5LaeA) was done in the fungus Aspergillus sp. Z5. Heterologous AnLaeA-and native Az5LaeA-overexpression exhibited similar phenotypic effects and caused an increase in production of a bioactive compound diorcinol in Aspergillus sp. Z5, which proved the conserved function of this global regulator. In particular, heteroexpression of AnLaeA showed a significant impact on the expression of velvet complex genes, diorcinol synthesis-related genes, and different transcription factors (TFs). Moreover, heteroexpression of AnLaeA influenced the whole genome gene expression of Aspergillus sp. Z5 and triggered the upregulation of many genes. Overall, these findings suggest that heteroexpression of AnLaeA in fungi serves as a simple and easy method to explore their metabolic potential. In relation to this, AnLaeA was overexpressed in the fungus Penicillium sp. LC1-4, which resulted in increased production of quinolactacin A.
Highlights
Marine fungi are a prolific source of discovering new drugs with tremendous bioactivities [1,2,3,4,5].Many studies revealed the noteworthiness of these microorganisms as a prospective resource of pharmaceutically important antifungal, antibacterial, antiviral, anti-inflammatory, anticancer, enzyme inhibitor, and antitumor compounds [6]
Filamentous fungi are a prospective resource of bioactive compounds
This study presents an attainable method based on utilizing the global regulator of secondary metabolism LaeA from A. nidulans as a molecular method based on utilizing the global regulator of secondary metabolism LaeA from A
Summary
Marine fungi are a prolific source of discovering new drugs with tremendous bioactivities [1,2,3,4,5].Many studies revealed the noteworthiness of these microorganisms as a prospective resource of pharmaceutically important antifungal, antibacterial, antiviral, anti-inflammatory, anticancer, enzyme inhibitor, and antitumor compounds [6]. Industrial investments in natural product research have decreased because conventional methods for the discovery of natural products cannot fulfil the increasing need of bioactive compounds in the healthcare system [7]. For instance, transcriptional regulation, epigenetic regulation, ribosome engineering, and heterologous expression, have been tested to analyze biosynthetic processes at different gene regulation levels in different fungi [8,9,10], but there is still a need to choose an attainable approach that could work in those unstudied fungi whose genomes are not explored. Global regulators regulate the expression of secondary metabolite (SM) biosynthetic gene clusters [7]. The discovery of global regulator LaeA in Aspergillus spp. by Bok and Keller has revolutionized the understanding of fungal secondary metabolism [11].
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