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Secondary Metabolites of the Rice Blast Fungus Pyricularia Oryzae: Biosynthesis and Biological Function

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International Journal of Molecular Sciences Review Secondary Metabolites of the Rice Blast Fungus Pyricularia oryzae: Biosynthesis and Biological Function Takayuki Motoyama Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama 351-0198, Japan; [email protected] Received: 31 August 2020; Accepted: 17 November 2020; Published: 18 November 2020 Abstract: Plant pathogenic fungi produce a wide variety of secondary metabolites with unique and complex structures. However, most fungal secondary metabolism genes are poorly expressed under laboratory conditions. Moreover, the relationship between pathogenicity and secondary metabolites remains unclear. To activate silent gene clusters in fungi, successful approaches such as epigenetic control, promoter exchange, and heterologous expression have been reported. Pyricularia oryzae, a well-characterized plant pathogenic fungus, is the causal pathogen of rice blast disease. P. oryzae is also rich in secondary metabolism genes. However, biosynthetic genes for only four groups of secondary metabolites have been well characterized in this fungus. Biosynthetic genes for two of the four groups of secondary metabolites have been identified by activating secondary metabolism. This review focuses on the biosynthesis and roles of the four groups of secondary metabolites produced by P. oryzae. These secondary metabolites include melanin, a polyketide compound required for rice infection; pyriculols, phytotoxic polyketide compounds; nectriapyrones, antibacterial polyketide compounds produced mainly by symbiotic fungi including endophytes and plant pathogens; and tenuazonic acid, a well-known mycotoxin produced by various plant pathogenic fungi and biosynthesized by a unique NRPS-PKS enzyme. Keywords: plant pathogenic fungus; Magnaporthe oryzae; secondary metabolite biosynthetic gene cluster; biological function 1. Introduction Filamentous fungi, including plant pathogenic fungi, produce a wide variety of secondary metabolites with unique and complex structures. However, the relationship between pathogenicity and secondary metabolites remains unclear in most cases. Filamentous fungi are a rich source of secondary metabolites for drug development. Whole-genome sequencing analyses have revealed that filamentous fungi possess many more secondary metabolism genes than expected, suggesting that most secondary metabolite biosynthetic genes are silent under laboratory conditions. To utilize fungal secondary metabolite production ability, secondary metabolism genes have been activated through many approaches, including epigenetic control, manipulation of global regulators, ribosome engineering, overexpression of pathway-specific transcription factors, co-culture, and heterologous expression of secondary metabolite gene clusters [1–4]. Pyricularia oryzae (syn. Magnaporthe oryzae) is the causal pathogen of rice blast disease and is a well-characterized plant pathogen. P. oryzae infects rice plants through an infection-specific organ, the appressorium, and proliferates inside the rice plant via filamentous growth and causes rice blast disease [5]. P. oryzae is also rich in secondary metabolism genes and shown to have 22 polyketide synthase (PKS) genes and eight non-ribosomal peptide synthetase (NRPS) genes [6,7]. Biosynthetic genes for only four groups of secondary metabolites (melanin, pyriculols, nectriapyrones, Int. J. Mol. Sci. 2020, 21, 8698; doi:10.3390/ijms21228698 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 2 of 17 tenuazonicInt. J. Mol. Sci. acid)2020, 21have, 8698 been well characterized in P. oryzae (Figure 1). Biosynthetic genes for 2two of 16 (nectryapyrones and tenuazonic acid) of the four groups of secondary metabolites have been identified by activating secondary metabolism. andHere, tenuazonic I review acid) the have biosynthesis been well and characterized biological inrolesP. oryzae of secondary(Figure1 ).metabolites Biosynthetic in genesthe rice for blast two fungus(nectryapyrones P. oryzae. andThis tenuazonic review mainly acid) focuses of the four on the groups four of groups secondary of secondary metabolites metabolites have been shown identified in Figureby activating 1. secondary metabolism. Figure 1. Chemical structures of secondary metabolites from the rice blast fungus P. oryzae. Figure 1. Chemical structures of secondary metabolites from the rice blast fungus P. oryzae. Here, I review the biosynthesis and biological roles of secondary metabolites in the rice blast 2. Melanin fungus P. oryzae. This review mainly focuses on the four groups of secondary metabolites shown in FigureP. oryzae1. produces the black pigment melanin (Figure 1), which is essential for rice infection [8]. Melanin is not a toxin, but this secondary metabolite is essential for infection by the mechanism shown2. Melanin below. P. oryzae forms an infection-specific organ, appressorium, and infects rice plants throughP.oryzae this organ.produces Appressorium the black pigment formation melanin and appressorium (Figure1), which melanin is essential formation for riceare essential infection for [ 8]. riceMelanin infection. is not The a invasion toxin, but of thisrice secondaryplants is achieved metabolite by an is infection essential peg for infectionthat is formed by the at mechanismthe base of anshown appressorium, below. P. oryzae whichforms adheres an infection-specific tightly to the ho organ,st surface. appressorium, For successful and infects penetration rice plants from through the infectionthis organ. peg, Appressoriummechanical force formation exerted by and appressori appressoriuma is necessary melanin [8]. formation An appressorial are essential melanin for layer rice betweeninfection. the The cell invasion wall and of cell rice membrane plants is achieved is required by for an infectionthe generation peg that of the is formed mechanical at the force. base ofThe an turgorappressorium, forces are which focused adheres toward tightly the epidermal to the host surfac surface.es of For the successful rice plant, penetration and the pressure from the inside infection the appressoriapeg, mechanical has been force estimated exerted by to appressoria be as high as is necessary8 MPa [9,10]. [8]. AnThis appressorial pressure can melanin be produced layer between by 3.2 Mthe glycerol cell wall andformed cell membraneinside the is requiredappressorium for the [1 generation1]. Melanin of the was mechanical proposed force. to Thefunction turgor forcesas a semipermeableare focused toward membrane the epidermal that passes surfaces water of but the not rice glycerol plant, and and the as pressure a structural inside support the appressoria for this very has highbeen pressure. estimated to be as high as 8 MPa [9,10]. This pressure can be produced by 3.2 M glycerol formed insideMelanin the appressorium is a well-known [11]. Melaninblack pi wasgment proposed of biological to function origin. as aOn semipermeablee type of fungal membrane melanin that is dihydroxynaphthalenepasses water but not glycerol (DHN)-melanin, and as a structural which is support biosynthesized for this very by highpolymerizing pressure. the polyketide compoundMelanin 1,8-dihydroxynaphthalene is a well-known black pigment(1,8-DHN) of biological[12,13]. P. origin. oryzae Oneproduces type ofDHN-melanin fungal melanin and is biosyntheticdihydroxynaphthalene genes have been (DHN)-melanin, identified, and which the bi isosynthetic biosynthesized pathway by has polymerizing been elucidated the polyketide(Figure 2) [14–17].compound The 1,8-dihydroxynaphthalenePKS enzyme ALB1/MGG_07219 (1,8-DHN) biosynthesizes [12,13]. P. oryzaethe backboneproduces compound DHN-melanin 1,3,6,8- and tetrahydroxynaphthalenebiosynthetic genes have (1,3,6,8-THN). been identified, Melanin and the was biosynthetic originally pathwayproposed has as beena pentaketide elucidated compound.(Figure2)[ 14However,–17]. The from PKS the enzyme analysis ALB1 of/MGG_07219 an ALB1 homolog biosynthesizes in a theclosely backbone related compound fungus, Colletotrichum1,3,6,8-tetrahydroxynaphthalene lagenarium, it has been (1,3,6,8-THN). shown that Melanin melanin was is originally a hexaketide proposed compound as a pentaketide and the backbonecompound. (1,3,6,8-THN) However, is frombiosynthesized the analysis using of an an acetyl-CoA ALB1 homolog and five in amalonyl-CoA closely related [18]. fungus,Then, 1,3,6,8-THNColletotrichum is lagenariumconverted, itto has 1,8-DHN been shown by using that melanin three enzymes: is a hexaketide 1,3,6,8-THN compound reductase and the (4HNR), backbone scytalone(1,3,6,8-THN) dehydratase is biosynthesized (SDH1/RSY1), using an and acetyl-CoA 1,3,8-trihydroxynaphthalene and five malonyl-CoA [18(1,3,8-THN)]. Then, 1,3,6,8-THN reductase is (3HNR/BUF1).converted to 1,8-DHN Finally, by1,8-DHN using threeis polymerized enzymes: 1,3,6,8-THNto form DHN-melanin. reductase (4HNR), Melanin scytalone biosynthesis dehydratase can be induced(SDH1/RSY1), by epigenetic and 1,3,8-trihydroxynaphthalene control [19]. (1,3,8-THN) reductase (3HNR/BUF1). Finally, 1,8-DHN is polymerized to form DHN-melanin. Melanin biosynthesis can be induced by epigenetic control [19]. Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 3 of 17 Int. J. Mol. Sci. 2020, 21, 8698 3 of 16 Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 3 of 17 acetyl-CoA acetyl-CoA+ 5 x malonyl-CoA+ Melanin 5 x malonyl-CoA Melanin PKS ALB1 MBI-P polymerization PKS ALB1 MBI-P polymerization 4HNR SDH1/RSY1 3HNR/BUF1 SDH1/RSY1 +3HNR4HNR SDH1/RSY1 +4HNR3HNR/BUF1 SDH1/RSY1 +3HNR +4HNR reduction -H2O
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