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Review
. 2022 Jul 15:10:901037.
doi: 10.3389/fbioe.2022.901037. eCollection 2022.

Transcriptional Activation of Biosynthetic Gene Clusters in Filamentous Fungi

László Mózsik  1 , Riccardo Iacovelli  1 , Roel A L Bovenberg  2   3 , Arnold J M Driessen  1
Affiliations
Review

Transcriptional Activation of Biosynthetic Gene Clusters in Filamentous Fungi

László Mózsik et al. Front Bioeng Biotechnol. .

Abstract

Filamentous fungi are highly productive cell factories, many of which are industrial producers of enzymes, organic acids, and secondary metabolites. The increasing number of sequenced fungal genomes revealed a vast and unexplored biosynthetic potential in the form of transcriptionally silent secondary metabolite biosynthetic gene clusters (BGCs). Various strategies have been carried out to explore and mine this untapped source of bioactive molecules, and with the advent of synthetic biology, novel applications, and tools have been developed for filamentous fungi. Here we summarize approaches aiming for the expression of endogenous or exogenous natural product BGCs, including synthetic transcription factors, assembly of artificial transcription units, gene cluster refactoring, fungal shuttle vectors, and platform strains.

Keywords: biosynthetic gene cluster; fungal platform strains; secondary metabilites; synthetic biology; synthetic transcriptional regulators.

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Conflict of interest statement

Author RALB was employed by the company DSM Biotechnology Center. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of a fungal biosynthetic gene cluster (BGCs) (A) and structurally different, representative members of nonribosomal peptides synthetase (NRPS), and polyketides synthase (PKS), terpenes synthase produced secondary metabolites and indole alkaloids from fungi (B).
FIGURE 2
FIGURE 2
Strategies for transcriptional activation for fungal biosynthetic gene clusters. Dashed arrows indicate native, solid arrows indicate engineered (strong or inducible) promoters.
See this image and copyright information in PMC

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