BAI Xiaoxuan, ZHANG Jifeng, LI Jing, et al. Advance on Transcription Factors Regulating the Synthesis of Secondary Metabolites Mediated by NRPS in Filamentous Fungi[J]. Science and Technology of Food Industry, 2024, 45(17): 445−453. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023090317.
Citation: BAI Xiaoxuan, ZHANG Jifeng, LI Jing, et al. Advance on Transcription Factors Regulating the Synthesis of Secondary Metabolites Mediated by NRPS in Filamentous Fungi[J]. Science and Technology of Food Industry, 2024, 45(17): 445−453. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023090317.

Advance on Transcription Factors Regulating the Synthesis of Secondary Metabolites Mediated by NRPS in Filamentous Fungi

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  • Received Date: September 27, 2023
  • Available Online: July 07, 2024
  • Secondary metabolites (SM) produced by filamentous fungi have been extensively applied in biomedicine, biological control, food, and other fields. The biosynthesis of most SMs is closely associated with the catalysis of non-ribosome peptide synthetase (NRPS), therefore the expression regulation of NRPS is crucial for SM biosynthesis. In order to further understand the expression regulation patterns of NRPS gene clusters in filamentous fungi, herein, the research progresses on the transcription factors regulating NRPS-mediated SM production are reviewed, of which both pathway-specific transcription factors and global transcription factors are individually descripted. The summarization is hoped to deepen the comprehension of NRPS-mediated SMs production regulated by transcription factors and provide a reference for development of natural products in filamentous fungi in the future.
  • [1]
    NARANJO-ORTIZ M A, GABALDÓN T. Fungal evolution:Diversity, taxonomy and phylogeny of the Fungi[J]. Fungal Biology Reviews,2019,94:2101−2137.
    [2]
    KELLER N P. Fungal secondary metabolism:regulation, function and drug discovery[J]. Nat Rev Microbiol,2019,17(3):167−180. doi: 10.1038/s41579-018-0121-1
    [3]
    VASSAUX A, MEUNIER L, VANDENBOL M, et al. Nonribosomal peptides in fungal cell factories:From genome mining to optimized heterologous production[J]. Biotechnol Adv,2019,37(8):107449. doi: 10.1016/j.biotechadv.2019.107449
    [4]
    PATEL K D, MACDONALD M R, AHMED S F, et al. Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases[J]. Nat Prod Rep,2023,51:1521.
    [5]
    SCHERLACH K, HERTWECK C. Mining and unearthing hidden biosynthetic potential[J]. Nat Commun,2021,12:3864. doi: 10.1038/s41467-021-24133-5
    [6]
    RUTLEDGE P J, CHALLIS G L. Discovery of microbial natural products by activation of silent biosynthetic gene clusters[J]. Nat Rev Microbiol,2015,13(8):509−523. doi: 10.1038/nrmicro3496
    [7]
    MIYANAGA A, KUDO F, EGUCHI T. Protein-protein interactions in polyketide synthase-nonribosomal peptide synthetase hybrid assembly lines[J]. Nat Prod Rep,2018,35(11):1185−1209. doi: 10.1039/C8NP00022K
    [8]
    BRAKHAGE A A. Regulation of fungal secondary metabolism[J]. Nat Rev Microbiol,2013,11(1):21−32. doi: 10.1038/nrmicro2916
    [9]
    LYU H N, LIU H W, KELLER N P, et al. Harnessing diverse transcriptional regulators for natural product discovery in fungi[J]. Nat Prod Rep,2020,37(1):6−16. doi: 10.1039/C8NP00027A
    [10]
    WANG W J, YU Y C, KELLER N P, et al. Presence, mode of action, and application of pathway specific transcription factors in Aspergillus biosynthetic gene clusters[J]. Int J Mol Sci,2021,22(16):8709. doi: 10.3390/ijms22168709
    [11]
    WALSH C T, O'BRIEN R V, KHOSLA C. Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds[J]. Angew Chem Int Ed,2013,52:7098−7124. doi: 10.1002/anie.201208344
    [12]
    SÜSSMUTH R D, MAINZ A. Nonribosomal peptide synthesis-principles and prospects[J]. Angew Chem Int Ed,2017,56(14):3770−3821. doi: 10.1002/anie.201609079
    [13]
    YANG X Q, FENG P, YIN Y, et al. Cyclosporine biosynthesis in Tolypocladium inflatum benefits fungal adaptation to the environment[J]. mBio,2018,9(5):e01211−18.
    [14]
    WANG G, LIU Z G, LIN R M, et al. Biosynthesis of antibiotic leucinostatins in bio-control fungus Purpureocillium lilacinum and their inhibition on phytophthora revealed by genome mining[J]. PLoS Pathog,2016,12(7):e1005685. doi: 10.1371/journal.ppat.1005685
    [15]
    JIN J M, LEE S, LEE J, et al. Functional characterization and manipulation of the apicidin biosynthetic pathway in Fusarium semitectum[J]. Mol Microbiol,2010,76(2):456−466. doi: 10.1111/j.1365-2958.2010.07109.x
    [16]
    NIEHAUS E M, JANEVSKA S, VON BARGEN K W, et al. Apicidin F:Characterization and genetic manipulation of a new secondary metabolite gene cluster in the rice pathogen Fusarium fujikuroi[J]. PLoS One,2014,9(7):e103336. doi: 10.1371/journal.pone.0103336
    [17]
    JIA L J, TANG H Y, WANG W Q, et al. A linear nonribosomal octapeptide from Fusarium graminearum facilitates cell-to-cell invasion of wheat[J]. Nat Commun,2019,10(1):922. doi: 10.1038/s41467-019-08726-9
    [18]
    BAHADOOR A, BRAUER E K, BOSNICH W, et al. Gramillin A and B:Cyclic lipopeptides identified as the nonribosomal biosynthetic products of Fusarium graminearum[J]. J Am Chem Soc,2018,140(48):16783−16791. doi: 10.1021/jacs.8b10017
    [19]
    杨晓钰, 何佳宁, 牛雪梅. 真菌中PKS-NRPS杂合天然产物研究进展[J]. 中国科学:生命科学,2019,49(7):848−864. [YANG X Y, HE J N, NIU X M. Research progress on fungal PKS-NRPS hybrid metabolites[J]. Scientia Sinica (Vitae),2019,49(7):848−864.] doi: 10.1360/SSV-2019-0105

    YANG X Y, HE J N, NIU X M. Research progress on fungal PKS-NRPS hybrid metabolites[J]. Scientia Sinica (Vitae), 2019, 49(7): 848−864. doi: 10.1360/SSV-2019-0105
    [20]
    PANG G, SUN T T, DING M Y, et al. Characterization of an exceptional fungal mutant enables the discovery of the specific regulator of a silent PKS-NRPS hybrid biosynthetic pathway[J]. J Agric Food Chem,2022,70(37):11769−11781. doi: 10.1021/acs.jafc.2c03550
    [21]
    JANEVSKA S, ARNDT B, BAUMANN L, et al. Establishment of the inducible tet-on system for the activation of the silent trichosetin gene cluster in Fusarium fujikuroi[J]. Toxins (Basel),2017,9(4):126. doi: 10.3390/toxins9040126
    [22]
    CHENG J T, WANG H M, YU J H, et al. Discovery of a potential liver fibrosis inhibitor from a mushroom endophytic fungus by genome mining of a silent biosynthetic gene cluster[J]. J Agric Food Chem,2021,69(38):11303−11310. doi: 10.1021/acs.jafc.1c03639
    [23]
    LI H, WEI H C, HU J Y, et al. Genomics-driven discovery of phytotoxic cytochalasans involved in the virulence of the wheat pathogen Parastagonospora nodorum[J]. ACS Chem Biol,2020,15(1):226−233. doi: 10.1021/acschembio.9b00791
    [24]
    CHENG M, ZHAO S S, LIU H, et al. Functional analysis of a chaetoglobosin A biosynthetic regulator in Chaetomium globosum[J]. Fungal Biol,2021,125(3):201−210. doi: 10.1016/j.funbio.2020.10.010
    [25]
    CARY J W, UKA V, HAN Z, et al. An Aspergillus flavus secondary metabolic gene cluster containing a hybrid PKS-NRPS is necessary for synthesis of the 2-pyridones, leporins[J]. Fungal Genet Biol,2015,81:88−97. doi: 10.1016/j.fgb.2015.05.010
    [26]
    CHEN B, SUN Y L, LI S Q, et al. Inductive production of the iron-chelating 2-pyridones benefits the producing fungus to compete for diverse niches[J]. mBio,2021,12(6):e327921.
    [27]
    SUN Y L, CHEN B, LI X L, et al. Orchestrated biosynthesis of the secondary metabolite cocktails enables the producing fungus to combat diverse bacteria[J]. mBio,2022,13(5):e180022.
    [28]
    TANG S, ZHANG W, LI Z M, et al. Discovery and characterization of a PKS-NRPS hybrid in Aspergillus terreus by genome mining[J]. J Nat Prod,2020,83(2):473−480. doi: 10.1021/acs.jnatprod.9b01140
    [29]
    HUANG X N, ZHANG W, TANG S, et al. Collaborative biosynthesis of a class of bioactive azaphilones by two separate gene clusters containing four PKS/NRPSs with transcriptional crosstalk in fungi[J]. Angew Chem Int Ed Engl,2020,59(11):4349−4353. doi: 10.1002/anie.201915514
    [30]
    YAO G S, BAI X F, ZHANG B X, et al. Enhanced production of terrein in marine-derived Aspergillus terreus by refactoring both global and pathway-specific transcription factors[J]. Microb Cell Fact,2022,21(1):136. doi: 10.1186/s12934-022-01859-5
    [31]
    HAUTBERGUE T, JAMIN E L, DEBRAUWER L, et al. From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites[J]. Nat Prod Rep,2018,35(2):147−173. doi: 10.1039/C7NP00032D
    [32]
    SHOSTAK K, BONNER C, SPROULE A, et al. Activation of biosynthetic gene clusters by the global transcriptional regulator TRI6 in Fusarium graminearum[J]. Mol Microbiol,2020,114(4):664−680. doi: 10.1111/mmi.14575
    [33]
    RÖSLER S M, SIEBER C M, HUMPF H U, et al. Interplay between pathway-specific and global regulation of the fumonisin gene cluster in the rice pathogen Fusarium fujikuroi[J]. Appl Microbiol Biotechnol,2016,100(13):5869−5882. doi: 10.1007/s00253-016-7426-7
    [34]
    BARDA O, MAOR U, SADHASIVAM S, et al. The pH-responsive transcription factor PacC governs pathogenicity and ochratoxin A biosynthesis in Aspergillus carbonarius[J]. Front Microbiol,2020,11:210. doi: 10.3389/fmicb.2020.00210
    [35]
    MERHEJ J, RICHARD-FORGET F, BARREAU C. The pH regulatory factor Pac1 regulates Tri gene expression and trichothecene production in Fusarium graminearum[J]. Fungal Genet Biol,2011,48(3):275−284. doi: 10.1016/j.fgb.2010.11.008
    [36]
    WANG B, HAN Z H, GONG D, et al. The pH signalling transcription factor PacC modulate growth, development, stress response and pathogenicity of Trichothecium roseum[J]. Environ Microbiol,2022,24(3):1608−1621. doi: 10.1111/1462-2920.15943
    [37]
    ZEHETBAUER F, SEIDL A, BERGER H, et al. RimO (SrrB) is required for carbon starvation signaling and production of secondary metabolites in Aspergillus nidulans[J]. Fungal Genet Biol,2022,162:103726. doi: 10.1016/j.fgb.2022.103726
    [38]
    RIES L, ALVES D C P, PEREIRA S L, et al. Aspergillus fumigatus acetate utilization impacts virulence traits and pathogenicity[J]. mBio,2021,12(4):e168221.
    [39]
    HOU R, JIANG C, ZHENG Q, et al. The AreA transcription factor mediates the regulation of deoxynivalenol (DON) synthesis by ammonium and cyclic adenosine monophosphate (cAMP) signalling in Fusarium graminearum[J]. Mol Plant Pathol,2015,16(9):987−999. doi: 10.1111/mpp.12254
    [40]
    YU Z Z, GAO J, IGBALAJOBI O, et al. The sulfur metabolism regulator MetR is a global regulator controlling phytochrome-dependent light responses in Aspergillus nidulans[J]. Sci Bull (Beijing),2021,66(6):592−602. doi: 10.1016/j.scib.2020.11.001
    [41]
    ZHANG G, YAN P, LENG D D, et al. Functional roles of LaeA-like genes in fungal growth, cellulase activity, and secondary metabolism in Pleurotus ostreatus[J]. J Fungi (Basel),2022,8(9):902. doi: 10.3390/jof8090902
    [42]
    WEI Z, SHU D, SUN Q, et al. The BcLAE1 is involved in the regulation of ABA biosynthesis in Botrytis cinerea TB-31[J]. Front Microbiol,2022,13:969499. doi: 10.3389/fmicb.2022.969499
    [43]
    REYES-DOMINGUEZ Y, BOK J W, BERGER H, et al. Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans[J]. Mol Microbiol,2010,76(6):1376−1386. doi: 10.1111/j.1365-2958.2010.07051.x
    [44]
    HUANG R L, DING R R, LIU Y, et al. GATA transcription factor WC2 regulates the biosynthesis of astaxanthin in yeast Xanthophyllomyces dendrorhous[J]. Microb Biotechnol,2022,15(10):2578−2593. doi: 10.1111/1751-7915.14115
    [45]
    DUSSART F, DOUGLAS R, SJÖKVIST E, et al. Genome-based discovery of polyketide-derived secondary metabolism pathways in the barley pathogen Ramularia collo-cygni[J]. Mol Plant Microbe Interact,2018,31(9):962−975. doi: 10.1094/MPMI-12-17-0299-R
    [46]
    PERRIN R M, FEDOROVA N D, BOK J W, et al. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA[J]. PLoS Pathog,2007,3(4):e50. doi: 10.1371/journal.ppat.0030050
    [47]
    FENG Y Q, YIN Z Y, WU Y X, et al. LaeA controls virulence and secondary metabolism in apple canker pathogen Valsa mali[J]. Front Microbiol,2020,11:581203. doi: 10.3389/fmicb.2020.581203
    [48]
    WANG K, CHI Z, LIU G L, et al. A novel PMA synthetase is the key enzyme for polymalate biosynthesis and its gene is regulated by a calcium signaling pathway in Aureobasidium melanogenum ATCC62921[J]. Int J Biol Macromol,2020,156:1053−1063. doi: 10.1016/j.ijbiomac.2019.11.188
    [49]
    QI C Y, JIA S L, LIU G L, et al. Polymalate (PMA) biosynthesis and its molecular regulation in Aureobasidium spp.[J]. Int J Biol Macromol,2021,174:512−518. doi: 10.1016/j.ijbiomac.2021.02.008
    [50]
    OAKLEY C E, AHUJA M, SUN W W, et al. Discovery of McrA, a master regulator of Aspergillus secondary metabolism[J]. Mol Microbiol,2017,103(2):347−365. doi: 10.1111/mmi.13562
    [51]
    GRAU M F, ENTWISTLE R, OAKLEY C E, et al. Overexpression of an LaeA-like methyltransferase upregulates secondary metabolite production in Aspergillus nidulans[J]. ACS Chem Biol,2019,14(7):1643−1651. doi: 10.1021/acschembio.9b00380
    [52]
    PERLATTI B, LAN N, JIANG Y Y, et al. Identification of secondary metabolites from Aspergillus pachycristatus by untargeted UPLC-ESI-HRMS/MS and genome mining[J]. Molecules,2020,25(4):913. doi: 10.3390/molecules25040913
    [53]
    GRESSLER M, ZAEHLE C, SCHERLACH K, et al. Multifactorial induction of an orphan PKS-NRPS gene cluster in Aspergillus terreus[J]. Chem Biol,2011,18(2):198−209. doi: 10.1016/j.chembiol.2010.12.011
    [54]
    GIL-SERNA J, GARCÍA-DÍAZ M, GONZÁLEZ-JAÉN M T, et al. Description of an orthologous cluster of ochratoxin A biosynthetic genes in Aspergillus and Penicillium species. A comparative analysis[J]. Int J Food Microbiol,2018,268:35−43. doi: 10.1016/j.ijfoodmicro.2017.12.028
    [55]
    WANG G, ZHANG H Y, WANG Y L, et al. Requirement of LaeA, VeA, and VelB on asexual development, ochratoxin A biosynthesis, and fungal virulence in Aspergillus ochraceus[J]. Front Microbiol,2019,10:2759. doi: 10.3389/fmicb.2019.02759
    [56]
    GERIN D, GARRAPA F, BALLESTER A R, et al. Functional role of Aspergillus carbonarius AcOTAbZIP Gene, a bZIP transcription factor within the OTA gene cluster[J]. Toxins,2021,13(2):111. doi: 10.3390/toxins13020111
    [57]
    WANG L M, JIN J, LIU X, et al. Effect of cinnamaldehyde on morphological alterations of Aspergillus ochraceus and expression of key genes involved in ochratoxin A biosynthesis[J]. Toxins (Basel),2018,10(9):340. doi: 10.3390/toxins10090340
    [58]
    CAI X Y, QI J R, XU Z, et al. Three stilbenes make difference to the antifungal effects on ochratoxin A and its precursor production of Aspergillus carbonarius[J]. Food Microbiol,2022,103:103967. doi: 10.1016/j.fm.2021.103967
    [59]
    WEI S, HU C J, ZHANG Y G, et al. AnAzf1 acts as a positive regulator of ochratoxin A biosynthesis in Aspergillus niger[J]. Appl Microbiol Biotechnol,2023,107(7-8):2501−2514. doi: 10.1007/s00253-023-12404-8
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