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Fungal P450 monooxygenases - the diversity in catalysis and their promising roles in biocontrol activity

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Abstract

The fungal P450s catalyze vital monooxygenation reactions in primary and secondary metabolism, which may lead to the production of diverse secondary metabolites. Many of these, such as from the family of trichothecenes, involve in biocontrol activities. The diversified nature of fungal P450 monooxygenases makes their host organisms adoptable to various ecological niches. The available genome data analysis provided an insight into the activity and mechanisms of the fungal P450s. However, still more structural and functional studies are needed to elucidate the details of its catalytic mechanism, and the advance studies are also required to decipher further about their dynamic role in various aspects of trichothecene oxygenations. This mini review will provide updated information on different fungal P450 monooxygenases, their genetic diversity, and their role in catalyzing various biochemical reactions leading to the production of plant growth promoting secondary metabolites.

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References

  • Akapo OO, Padayachee T, Chen W, Kappo AP, Yu J-H, Nelson DR, Syed K (2019) Distribution and diversity of cytochrome P450 monooxygenases in the fungal class tremellomycetes. Int J Mol Sci 20:2889

    PubMed Central  Google Scholar 

  • Altun A, Shaik S, Thiel W (2007) What is the active species of cytochrome P450 during camphor hydroxylation? QM/MM studies of different electronic states of compound I and of reduced and oxidized iron− oxo intermediates. J Am Chem Soc 129:8978–8987

    CAS  PubMed  Google Scholar 

  • Batabyal D, Richards LS, Poulos TL (2017) Effect of redox partner binding on cytochrome P450 conformational dynamics. J Am Chem Soc 139:13193–13199

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cardoza RE, Malmierca MG, Hermosa MR, Alexander NJ, McCormick SP, Proctor RH, Tijerino AM, Rumbero A, Monte E, Gutiérrez S (2011) Identification of loci and functional characterization of trichothecene biosynthesis genes in filamentous fungi of the genus Trichoderma. Appl Environ Microbiol 77:4867–4877

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cardoza RE, McCormick SP, Lindo L, Kim H-S, Olivera ER, Nelson DR, Proctor RH, Gutiérrez S (2019) A cytochrome P450 monooxygenase gene required for biosynthesis of the trichothecene toxin harzianum a in Trichoderma. Appl Microbiol Biotechnol 1–17

  • Carpenter MA, Ridgway HJ, Stringer AM, Hay AJ, Stewart A (2008) Characterisation of a Trichoderma hamatum monooxygenase gene involved in antagonistic activity against fungal plant pathogens. Curr Genet 53:193–205

    CAS  PubMed  Google Scholar 

  • Chadha S, Mehetre ST, Bansal R, Kuo A, Aerts A, Grigoriev IV, Druzhinina IS, Mukherjee PK (2018) Genome-wide analysis of cytochrome P450s of Trichoderma spp.: annotation and evolutionary relationships. Fungal biol Biotechnol 5:12

    PubMed  PubMed Central  Google Scholar 

  • Chen W, Lee M-K, Jefcoate C, Kim S-C, Chen F, Yu J-H (2014) Fungal cytochrome p450 monooxygenases: their distribution, structure, functions, family expansion, and evolutionary origin. Genome Biol Evol 6:1620–1634

    PubMed  PubMed Central  Google Scholar 

  • Chooi Y-H, Hong YJ, Cacho RA, Tantillo DJ, Tang Y (2013) A cytochrome P450 serves as an unexpected terpene cyclase during fungal meroterpenoid biosynthesis. J Am Chem Soc 135:16805–16808

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coelho PS, Brustad EM, Kannan A, Arnold FH (2013) Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes. Science (80- ) 339:307–310

    PubMed  Google Scholar 

  • Córdova P, Gonzalez A-M, Nelson DR, Gutiérrez M-S, Baeza M, Cifuentes V, Alcaíno J (2017) Characterization of the cytochrome P450 monooxygenase genes (P450ome) from the carotenogenic yeast Xanthophyllomyces dendrorhous. BMC Genomics 18:540

    PubMed  PubMed Central  Google Scholar 

  • Črešnar B, Petrič Š (2011) Cytochrome P450 enzymes in the fungal kingdom. Biochim Biophys Acta (BBA)-proteins Proteomics 1814:29–35

    Google Scholar 

  • Cui C-B, Kakeya H, Osada H (1996) Spirotryprostatin B, a novel mammalian cell cycle inhibitor produced by Aspergillus fumigatus. J Antibiot (Tokyo) 49:832–835

    CAS  Google Scholar 

  • Danielson PB (2002) The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr Drug Metab 3:561–597

    CAS  PubMed  Google Scholar 

  • Del Carratore R, Gervasi PG, Contini MP, Beffy P, Maserti BE, Giovannetti G, Brondolo A, Longo V (2011) Expression and characterization of two new alkane-inducible cytochrome P450s from Trichoderma harzianum. Biotechnol Lett 33:1201–1206

    PubMed  Google Scholar 

  • Deng J, Carbone I, Dean RA (2007) The evolutionary history of cytochrome P450 genes in four filamentous Ascomycetes. BMC Evol Biol 7:30

    PubMed  PubMed Central  Google Scholar 

  • Dubey KD, Shaik S (2019) Cytochrome P450—the wonderful nanomachine revealed through dynamic simulations of the catalytic cycle. Acc Chem Res 52:389–399

    PubMed  Google Scholar 

  • Groves JT (2014) Enzymatic C–H bond activation: using push to get pull. Nat Chem 6:89

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guengerich FP (2009) Cataloging the repertoire of Nature’s blowtorch, P450. Chem Biol 16:1215–1216

    CAS  PubMed  Google Scholar 

  • Halo LM, Heneghan MN, Yakasai AA, Song Z, Williams K, Bailey AM, Cox RJ, Lazarus CM, Simpson TJ (2008) Late stage oxidations during the biosynthesis of the 2-pyridone tenellin in the entomopathogenic fungus Beauveria bassiana. J Am Chem Soc 130:17988–17996

    CAS  PubMed  Google Scholar 

  • Hannemann F, Bichet A, Ewen KM, Bernhardt R (2007) Cytochrome P450 systems—biological variations of electron transport chains. Biochim Biophys Acta (BBA)-general subj 1770:330–344

    CAS  Google Scholar 

  • Hlavica P (2013) Evaluation of structural features in fungal cytochromes P450 predicted to rule catalytic diversification. Biochim Biophys Acta (BBA)-proteins proteomics 1834:205–220

    CAS  Google Scholar 

  • Hohn TM, Desjardins AE, McCormick SP (1995) TheTri4 gene of Fusarium sporotrichioides encodes a cytochrome P450 monooxygenase involved in trichothecene biosynthesis. Mol Gen Genet MGG 248:95–102

    CAS  PubMed  Google Scholar 

  • Hussain R, Ahmed M, Khan TA, Akhter Y (2018) Augmentation of cytochrome P450 monooxygenase catalysis on its interaction with NADPH-cytochrome P450 reductase FMN domain from Trichoderma brevicompactum. Int J Biochem Cell Biol 103:74–80

    CAS  PubMed  Google Scholar 

  • Hussain R, Kumari I, Sharma S, Ahmed M, Khan TA, Akhter Y (2017) Catalytic diversity and homotropic allostery of two cytochrome P450 monooxygenase like proteins from Trichoderma brevicompactum. JBIC J Biol Inorg Chem 22:1197–1209

    CAS  PubMed  Google Scholar 

  • Jawallapersand P, Mashele SS, Kovačič L, Stojan J, Komel R, Pakala SB, Kraševec N, Syed K (2014) Cytochrome P450 monooxygenase CYP53 family in fungi: comparative structural and evolutionary analysis and its role as a common alternative anti-fungal drug target. PLoS One 9:e107209

    PubMed  PubMed Central  Google Scholar 

  • Ji L, Zhang J, Liu W, de Visser SP (2014) Metabolism of halogenated alkanes by cytochrome P450 enzymes. Aerobic oxidation versus anaerobic reduction. Chem Asian J 9:1175–1182

    CAS  PubMed  Google Scholar 

  • Lin H-C, Tsunematsu Y, Dhingra S, Xu W, Fukutomi M, Chooi Y-H, Cane DE, Calvo AM, Watanabe K, Tang Y (2014) Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J Am Chem Soc 136:4426–4436

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malmierca MG, Cardoza RE, Alexander NJ, McCormick SP, Hermosa R, Monte E, Gutiérrez S (2012) Involvement of Trichoderma trichothecenes in the biocontrol activity and induction of plant defense-related genes. Appl Environ Microbiol 78:4856–4868

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matowane RG, Wieteska L, Bamal HD, Kgosiemang IKR, Van Wyk M, Manume NA, Abdalla SMH, Mashele SS, Gront D, Syed K (2018) In silico analysis of cytochrome P450 monooxygenases in chronic granulomatous infectious fungus Sporothrix schenckii: special focus on CYP51. Biochim Biophys Acta (BBA)-proteins proteomics 1866:166–177

    CAS  Google Scholar 

  • Mazzaferro LS, Hüttel W, Fries A, Müller M (2015) Cytochrome P450-catalyzed regio-and stereoselective phenol coupling of fungal natural products. J Am Chem Soc 137:12289–12295

    CAS  PubMed  Google Scholar 

  • McCormick SP, Alexander NJ, Proctor RH (2006) Fusarium Tri4 encodes a multifunctional oxygenase required for trichothecene biosynthesis. Can J Microbiol 52:636–642

    CAS  PubMed  Google Scholar 

  • McLean KJ, Luciakova D, Belcher J, Tee KL, Munro AW (2015) Biological diversity of cytochrome P450 redox partner systems. In: Monooxygenase, peroxidase and peroxygenase properties and mechanisms of cytochrome P450. Springer, pp 299–317

  • Moktali V, Park J, Fedorova-Abrams ND, Park B, Choi J, Lee Y-H, Kang S (2012) Systematic and searchable classification of cytochrome P450 proteins encoded by fungal and oomycete genomes. BMC Genomics 13:525

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherjee PK, Horwitz BA, Kenerley CM (2012) Secondary metabolism in Trichoderma–a genomic perspective. Microbiology 158:35–45

    CAS  PubMed  Google Scholar 

  • Nelson DR (1999) Cytochrome P450 and the individuality of species. Arch Biochem Biophys 369:1–10

    CAS  PubMed  Google Scholar 

  • Nelson DR (2009) The cytochrome p450 homepage. Hum Genomics 4:59

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson DR (2018) Cytochrome P450 diversity in the tree of life. Biochim Biophys Acta (BBA)-proteins Proteomics 1866:141–154

    CAS  Google Scholar 

  • Ngwenya M, Chen W, Basson A, Shandu J, Yu J-H, Nelson D, Syed K (2018) Blooming of unusual cytochrome P450s by tandem duplication in the pathogenic fungus Conidiobolus coronatus. Int J Mol Sci 19:1711

    PubMed Central  Google Scholar 

  • O’Reilly E, Köhler V, Flitsch SL, Turner NJ (2011) Cytochromes P450 as useful biocatalysts: addressing the limitations. Chem Commun 47:2490–2501

    Google Scholar 

  • Ortiz de Montellano PR (2009) Hydrocarbon hydroxylation by cytochrome P450 enzymes. Chem Rev 110:932–948

    Google Scholar 

  • Park J, Lee S, Choi J, Ahn K, Park B, Park J, Kang S, Lee Y-H (2008) Fungal cytochrome P450 database. BMC Genomics 9:402

    PubMed  PubMed Central  Google Scholar 

  • Postils V, Saint-André M, Timmins A, Li X-X, Wang Y, Luis J, Solà M, de Visser S (2018) Quantum mechanics/molecular mechanics studies on the relative reactivities of compound I and II in cytochrome P450 enzymes. Int J Mol Sci 19:1974

    PubMed Central  Google Scholar 

  • Proctor RH, McCormick SP, Kim H-S, Cardoza RE, Stanley AM, Lindo L, Kelly A, Brown DW, Lee T, Vaughan MM (2018) Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi. PLoS Pathog 14:e1006946

    PubMed  PubMed Central  Google Scholar 

  • Qhanya LB, Matowane G, Chen W, Sun Y, Letsimo EM, Parvez M, Yu J-H, Mashele SS, Syed K (2015) Genome-wide annotation and comparative analysis of cytochrome P450 monooxygenases in Basidiomycete biotrophic plant pathogens. PLoS One 10:e0142100

    PubMed  PubMed Central  Google Scholar 

  • Ramírez-Valdespino CA, Porras-Troncoso MD, Corrales-Escobosa AR, Wrobel K, Martínez-Hernández P, Olmedo-Monfil V (2017) Functional characterization of TvCyt2, a member of the p450 monooxygenases from Trichoderma virens relevant during the association with plants and mycoparasitism. Mol Plant-Microbe Interact 31:289–298

    PubMed  Google Scholar 

  • Riplinger C, Bill E, Daiber A, Ullrich V, Shoun H, Neese F (2014) New insights into the nature of observable reaction intermediates in cytochrome P450 NO reductase by using a combination of spectroscopy and quantum mechanics/molecular mechanics calculations. Chem Eur J 20:1602–1614

    CAS  PubMed  Google Scholar 

  • Riplinger C, Neese F (2011) The reaction mechanism of cytochrome P450 NO reductase: a detailed quantum mechanics/molecular mechanics study. ChemPhysChem 12:3192–3203

    CAS  PubMed  Google Scholar 

  • Roccatano D (2015) Structure, dynamics, and function of the monooxygenase P450 BM-3: insights from computer simulations studies. J Phys Condens Matter 27:273102

    PubMed  Google Scholar 

  • Sainna MA, Kumar S, Kumar D, Fornarini S, Crestoni ME, de Visser SP (2015) A comprehensive test set of epoxidation rate constants for iron (iv)–oxo porphyrin cation radical complexes. Chem Sci 6:1516–1529

    CAS  PubMed  Google Scholar 

  • Sawada Y, Ayabe S (2005) Multiple mutagenesis of P450 isoflavonoid synthase reveals a key active-site residue. Biochem Biophys Res Commun 330:907–913

    CAS  PubMed  Google Scholar 

  • Schulz S, Schumacher D, Raszkowski D, Girhard M, Urlacher VB (2016) Fusion to hydrophobin hFBi improves the catalytic performance of a cytochrome P450 system. Front Bioeng Biotechnol 4:57

    PubMed  PubMed Central  Google Scholar 

  • Seifert A, Pleiss J (2009) Identification of selectivity-determining residues in cytochrome P450 monooxygenases: a systematic analysis of the substrate recognition site 5. Proteins Struct Funct Bioinforma 74:1028–1035

    CAS  Google Scholar 

  • Sello MM, Jafta N, Nelson DR, Chen W, Yu J-H, Parvez M, Kgosiemang IKR, Monyaki R, Raselemane SC, Qhanya LB (2015) Diversity and evolution of cytochrome P450 monooxygenases in oomycetes. Sci Rep 5:11572

    PubMed  PubMed Central  Google Scholar 

  • Shin J, Kim J-E, Lee Y-W, Son H (2018) Fungal cytochrome P450s and the P450 complement (CYPome) of Fusarium graminearum. Toxins (Basel) 10:112

    Google Scholar 

  • Sono M, Roach MP, Coulter ED, Dawson JH (1996) Heme-containing oxygenases. Chem Rev 96:2841–2888

    CAS  PubMed  Google Scholar 

  • Syed K, Mashele SS (2014) Comparative analysis of P450 signature motifs EXXR and CXG in the large and diverse kingdom of fungi: identification of evolutionarily conserved amino acid patterns characteristic of P450 family. PLoS One 9:e95616

    PubMed  PubMed Central  Google Scholar 

  • Takahashi S, Uchida K, Kakinuma N, Hashimoto R, Yanagisawa T, Nakagawa A (1998) The structures of pyridovericin and pyridomacrolidin, new metabolites from the entomopathogenic fungus, Beauveria bassiana. J Antibiot (Tokyo) 51:1051–1054

    CAS  Google Scholar 

  • Tokai T, Koshino H, Takahashi-Ando N, Sato M, Fujimura M, Kimura M (2007) Fusarium Tri4 encodes a key multifunctional cytochrome P450 monooxygenase for four consecutive oxygenation steps in trichothecene biosynthesis. Biochem Biophys Res Commun 353:412–417

    CAS  PubMed  Google Scholar 

  • Urlacher VB (2010) Catalysis with cytochrome P 450 monooxygenases. Handb Green Chem Online:1–25

  • Urlacher VB, Girhard M (2019) Cytochrome p450 monooxygenases in biotechnology and synthetic biology. Trends Biotechnol

  • Urlacher VB, Girhard M (2012) Cytochrome P450 monooxygenases: an update on perspectives for synthetic application. Trends Biotechnol 30:26–36

    CAS  PubMed  Google Scholar 

  • Wang X-Y, Yan H-M, Han Y-L, Zhang Z-X, Zhang X-Y, Yang W-J, Guo Z, Li Y-R (2018) Do two oxidants (ferric-peroxo and ferryl-oxo species) act in the biosynthesis of estrogens? A DFT calculation. RSC Adv 8:15196–15201

    CAS  Google Scholar 

  • Zhang X, Li S (2017) Expansion of chemical space for natural products by uncommon P450 reactions. Nat Prod Rep 34:1061–1089

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are thankful to Bioinformatics Resources & Applications Facility, Centre for Development in Advanced Computing, Pune for providing the computational infrastructure.

Funding

National Fellowship for Higher Education to RH from University Grants Commission, Govt. of India (UGC) is acknowledged. YA lab is supported by extramural research funds from Indian Council of Medical Research (Ministry of Health & Family welfare, Government of India) and Department of Biotechnology (Ministry of Science & Technology, Government of India).

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Authors and Affiliations

  1. Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India

    Razak Hussain & Tabreiz Ahmad Khan

  2. Department of Environmental Science, School of Earth and Environmental Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh, 176206, India

    Mushtaq Ahmed

  3. Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, Uttar Pradesh, 226025, India

    Yusuf Akhter

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  1. Razak Hussain
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Correspondence to Yusuf Akhter.

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Hussain, R., Ahmed, M., Khan, T.A. et al. Fungal P450 monooxygenases - the diversity in catalysis and their promising roles in biocontrol activity. Appl Microbiol Biotechnol 104, 989–999 (2020). https://doi.org/10.1007/s00253-019-10305-3

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