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Review
. 2022 Dec 20:13:1070110.
doi: 10.3389/fmicb.2022.1070110. eCollection 2022.

Advances and perspectives on perylenequinone biosynthesis

Huaxiang Deng  1   2 , Xinxin Liang  2 , Jinbin Liu  3 , Xiaohui Zheng  4 , Tai-Ping Fan  5 , Yujie Cai  2
Affiliations
Review

Advances and perspectives on perylenequinone biosynthesis

Huaxiang Deng et al. Front Microbiol. .

Abstract

Under illumination, the fungal secondary metabolites, perylenequinones (PQs) react with molecular oxygen to generate reactive oxygen species (ROS), which, in excess can damage cellular macromolecules and trigger apoptosis. Based on this property, PQs have been widely used as photosensitizers and applied in pharmaceuticals, which has stimulated research into the discovery of new PQs and the elucidation of their biosynthetic pathways. The PQs-associated literature covering from April 1967 to September 2022 is reviewed in three sections: (1) the sources, structural diversity, and biological activities of microbial PQs; (2) elucidation of PQ biosynthetic pathways, associated genes, and mechanisms of regulation; and (3) advances in pathway engineering and future potential strategies to modify cellular metabolism and improve PQ production.

Keywords: automatic engineering; high throughput tools; metabolite orchestration; metabolite platform; pathway deciphering; perylenequinones.

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Conflict of interest statement

The 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
Methods for confirming perylenequinone-associated genes and pathways. (A) Homologous PQs-associated biosynthetic gene clusters. (B) For this split-marker approach, we need to synthesize two nucleotides fragment I and II. Fragments I comprise a partial selective marker and a sequence homologous to 5′ target locus; fragments II contain a partial selective marker and a sequence homologous to 3′ target locus. Thus, 5′ and 3′ homologous arms facilitate relevant homologous recombination of target genes and mutants can be screened on antibiotic regeneration plates due to the overlapping sequences of the selective marker of two fragments. (C) The CRISPR system contains two crucial elements, including Cas9 nuclease and sgRNA. The complex of these two elements precisely triggers double-strand breaks, induces cellular repair pathways, and results in relevant gene modification. (D) Verification of crucial PQs-associated genes by expressing them in the tractable microorganisms and then following chemical comparisons.
Figure 2
Figure 2
Schematic representation of perylenequinone flux using glucose as the original substrate.
Figure 3
Figure 3
Diverse strategies to activate or broaden perylenequinone pools. (A) Activate the perylenequinone pathway by overexpressing pathway-specificity transcriptional factors. (B) Activate the perylenequinone pathway by engineering epigenetic regulators. (C) Enhance the perylenequinone pathway by increasing the central pathway. (D) Enhance the perylenequinone pathway by signal pathways. Environmental, chemical and physical signals trigger relevant global regulators, which regulate perylenequinone-linked genes by activating these genes. (E) Construct a diverse perylenequinone platform in tractable Aspergillus species. (F) Improve the perylenequinone pathway by microorganism co-culture, including bacteria-fungi co-cultures and fungi-fungi co-cultures.
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