Pinmei Wang
Hee-Soo Park
Wenjie Wang
Wen-Bing Yin- 1Ocean College, Zhejiang University, Zhoushan, China
- 2School of Food Science and Biotechnology, Kyungpook National University, Daegu, Republic of Korea
- 3School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
- 4State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Editorial on the Research Topic
Gene regulation of fungal secondary metabolism
Fungi are prolific producers of secondary metabolites (SMs), which encompass a wide range of low-molecular-mass compounds. These SMs serve essential functions such as defense against pathogens, inhibition of competing microorganisms, and intercellular communication (Keller, 2019; Yu et al., 2023). Therefore, SMs usually possess dual roles, hazardous mycotoxins (e.g., aflatoxin and patulin), and valuable pharmaceuticals (e.g., penicillin and lovastatin) (Wang et al., 2021b). Surprisingly, genome mining studies have unveiled that the potential of fungi to synthesize SMs has been greatly underestimated, as numerous of biosynthetic gene clusters (BGCs) remain silent or cryptic under laboratory culture conditions (Brakhage, 2013; Wang et al., 2021b). Transcription factors (TFs) play an essential regulatory role in the expression of SM genes (Yin and Keller, 2011; Keller, 2019; Wang et al., 2021a). In recent years, researchers have actively explored the gene regulation mechanism of fungal secondary metabolism by using the methods of genetics, molecular biology and biochemistry (Wang et al., 2022; Zhang et al., 2022; Wei et al., 2023). The aim of this Research Topic is to gain a better understanding of the regulatory elements and network of fungal SMs, providing genetic approaches to manipulate fungal secondary metabolism to produce novel compounds with beneficial properties for medicine, agriculture, and other applications.
This Research Topic contains one review paper and eight original research articles. Deng et al. review article presents a comprehensive summary of perylenequinones (PQs) with literatures spanning from 1967 to 2022. As photosensitizers, PQs have been applied in various fields, including medical, food, agricultural and manufacturing fields. The authors not only collected information of the sources, structure diversity and biological activities of PQs, but also the biosynthetic pathways and regulation mechanism. Besides, strategies are given to enhance PQ production and quality, including modulating regulatory mechanisms, coordinating signal-response pathways, constructing heterologous production platforms, and applying physical and chemical methods to stimulate biosynthesis.
Three research articles investigate the gene regulation of ganoderma triterpenoids (GTs) biosynthesis in Ganoderma lucidum and Ganoderma lingzhi, both of which are traditional Chinese medicines. GTs exhibit a variety of biological activities, and their biosynthesis is regulated through a complex interplay between environmental and genetic factors. Meng et al. employed a comprehensive approach involving transcriptome and metabolome analyses to investigate the transcription factors (TFs) involved in ganoderic acid (GA) biosynthesis in different developmental stages of G. lucidum. By comparing gene expression patterns, they identified that homeobox transcription factor and velvet family protein were responsible for GA biosynthesis, and provided a model for the involvement of TFs in GA biosynthesis during fruiting body formation. The research article by Luo et al. describes an essential function of the well-known methyltransferase LaeA in the regulation of GA in basidiomycete fungus G. lingzhi. The results of laeA gene deletion and overexpression suggested that LaeA could regulate the expression of GA biosynthetic genes and asexual sporulation. The study by Xu et al. focused on understanding how G. lucidum responds to methyl jasmonate, an important elicitor in inducing the production of triterpenes and the biomass of mycelia. Transcriptomic analysis allowed researchers to identify positive and negative transcription factors of GTs that response to methyl jasmonate, and a negative regulator gene Glmhr1 was found. The study provides new insights into the molecular mechanisms underlying the response of G. lucidum to fungal hormones and may facilitate the development of new strategies for enhancing the production of bioactive compounds.
Other two studies explored the role of BcLAE1 and Bcfrp1 in the regulation of abscisic acid (ABA) biosynthesis and growth of Botrytis cinerea. The study conducted by Wei et al. demonstrated the significant role of the methyltransferase BcLAE1 in epigenetic regulation of ABA biosynthesis in B. cinerea. Chen et al. elucidated the positive role and molecular mechanism of an F-box protein Bcfrp1 in regulating ABA biosynthesis and fungal growth. These studies provide valuable insights into the molecular mechanisms involving the regulation of ABA biosynthesis in B. cinerea.
Additionally, two separate investigations have provided knowledge about the mechanisms governing microbe-microbe interactions and plant-microbe interactions, respectively. Brault et al. conducted a study revealing the crucial role of Sib proteins (Sib1, Sib2, and Sib3) in facilitating iron acquisition and cross-feeding interaction between Schizosaccharomyces pombe and Saccharomyces cerevisiae. These proteins are responsible for the transport of ferrichrome, and their knockout disrupted the transport process and hindered cross-feeding. In another article by Wu et al., they investigated the production and distribution of flavonoids by the endophytic fungus Aspergillus sp. Gbtc 2, which was isolated from the root of Ginkgo biloba. Through LC-MS analysis, they identified flavonoid metabolites and discovered a unique distribution pattern of these compounds, both intracellularly and extracellularly, within the fungus Gbtc 2. This research expands our understanding of the potential application of endophytic fungi in the industrial flavonoid production. In the study conducted by Wang et al., genomic alterations in Fusarium proliferatum strains were examined to understand their role in adaptation and fumonisin production. Through their analysis, a total of 121 distinct genomic loci were identified, implicating 85 potential genes involved in adaptation to diverse environments and fumonisin B1 (FB1) production. Notably, five candidate genes were identified as being closely associated with FB1 production.
The articles within this Research Topic collectively highlight the significance of gene regulation in the biosynthesis of secondary metabolites in fungi. By investigating the regulatory mechanisms governing these processes, researchers can attain a comprehensive comprehension of the molecular mechanisms underlying fungal secondary metabolism. Moreover, these studies enable the identification of potential targets for genetic engineering, aiming to augment the production of bioactive compounds by these organisms. Such findings carry significant implications across various fields including medicine, agriculture, and biotechnology, as they contribute to the exploration and development of novel bioactive compounds of interest.
Author contributions
PW: Writing—original draft. H-SP: Writing—review and editing. WW: Writing—review and editing. W-BY: Writing—review and editing.
Funding
This research was supported in part by National Natural Science Foundation of China (32170066), the Key Laboratory of Tropical Marine Ecosystem and Bioresource, MNR (2022QN02) and Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City (420LH004), Key Research Program of Frontier Sciences, Chinese Academy of Sciences (ZDBS-LY-SM016), Biological Resources Program, Chinese Academy of Sciences (KFJ-BRP-009-005), and National Research Foundation of Korea (NRF) grant (NRF-2020R1C1C1004473).
Conflict of interest
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.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
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Keller, N.P. (2019). Fungal secondary metabolism: regulation, function and drug discovery. Nat. Rev. Microbiol. 17, 167–180. doi: 10.1038/s41579-018-0121-1
Wang, G., Ran, H., Fan, J., Keller, N.P., Liu, Z., Wu, F., et al. (2022). Fungal-fungal cocultivation leads to widespread secondary metabolite alteration requiring the partial loss-of-function VeA1 protein. Sci. Adv. 8, eabo6094. doi: 10.1126/sciadv.abo6094
Wang, W., Yu, Y., Keller, N.P., and Wang, P. (2021a). Presence, mode of action, and application of pathway specific transcription factors in Aspergillus biosynthetic gene clusters. Int. J. Mol. Sci. 22, 8709. doi: 10.3390/ijms22168709
Wang, W.J., Drott, M., Greco, C., Luciano-Rosario, D., Wang, P.M., and Keller, N.P. (2021b). Transcription factor repurposing offers insights into evolution of biosynthetic gene cluster regulation. Mbio 12, 10–1128. doi: 10.1128/mBio.01399-21
Wei, P.L., Fan, J., Yu, J., Ma, Z., Guo, X., Keller, N.P., et al. (2023). Quantitative characterization of filamentous fungal promoters on a single-cell resolution to discover cryptic natural products. Sci. China Life Sci. 66, 848–860. doi: 10.1007/s11427-022-2175-0
Yin, W., and Keller, N.P. (2011). Transcriptional regulatory elements in fungal secondary metabolism. J. Microbiol. 49, 329–339. doi: 10.1007/s12275-011-1009-1
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Keywords: gene regulation, transcription factors, fungal secondary metabolism, biosynthesis, secondary metabolites
Citation: Wang P, Park H-S, Wang W and Yin W-B (2023) Editorial: Gene regulation of fungal secondary metabolism. Front. Microbiol. 14:1260849. doi: 10.3389/fmicb.2023.1260849
Received: 18 July 2023; Accepted: 07 August 2023;
Published: 15 August 2023.
Edited and reviewed by: Biswarup Mukhopadhyay, Virginia Tech, United States
Copyright © 2023 Wang, Park, Wang and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Pinmei Wang, wangpinmei@zju.edu.cn; Wen-Bing Yin, yinwb@im.ac.cn