Cercosporin

Cercosporin
Names
	IUPAC name 7,19-dihydroxy-5,21-bis(2-hydroxypropyl)-6,20-dimethoxy-12,14-dioxahexacyclo[13.8.0.02,11.03,8.04,22.018,23]tricosa-1,3(8),4,6,10,15,18(23),19,21-nonaene-9,17-dione
Identifiers
CAS Number	35082-49-6;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:91878;
ChEMBL	ChEMBL1080283;
ChemSpider	2573;
PubChem CID	2674;
UNII	DK0O6YH55G;
	InChI InChI=1S/C29H26O10/c1-10(30)5-12-18-19-13(6-11(2)31)29(37-4)27(35)21-15(33)8-17-23(25(19)21)22-16(38-9-39-17)7-14(32)20(24(18)22)26(34)28(12)36-3/h7-8,10-11,30-31,34-35H,5-6,9H2,1-4H3 Key: MXLWQNCWIIZUQT-UHFFFAOYSA-N;
	SMILES CC(CC1=C2C3=C(C(=C(C4=C3C5=C6C2=C(C(=O)C=C6OCOC5=CC4=O)C(=C1OC)O)O)OC)CC(C)O)O;
Properties
Chemical formula	C29H26O10
Molar mass	534.517 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Cercosporin is a red toxin created by the fungal genus Cercospora. Cercospora act as pathogens on a variety of plants including corn, tobacco, soybean, and coffee.^[1] Cercosporin is a perylenequinone natural product^[2]^[3] that is photoactivated and uses reactive oxygen species (ROS) to damage cell components (membranes, proteins, lipids, etc.).^[4]

Biosynthesis

Light is required for biosynthesis and activation of cercosporin, and it has been demonstrated that light, temperature, and culture medium are regulating factors in the production of cercosporin.^[5]

Cercosporin is biosynthesized via polyketide synthases, and there are several genes that have been found responsible in the creation of the natural product.^[4]^[6] Overall, there are 8 CTB enzymes (CTB1-8) that contribute to the production of cercosporin.^[4] CTB1 (cercosporin toxin biosynthesis) is a non-reducing PKS consisting of a KS, AT, TE/CYC and 2 ACP domains that are vital in the initiation of the creation of cercosporin.^[6] The other CTB enzymes are not as well studied, but play important roles in the biosynthesis. CTB2 acts as a methyl transferase, CTB3 also functions as a methyl transferase but also functions as a FAD-dependent monoxygenase, CTB4 is a MFS transporter, CTB5 is a FAD-dependent oxidoreductase, CTB6 is a NADPH-dependent ketone reductase, CTB7 is another FAD-dependent monoxygenase, and CTB8 is a transcription factor that regulates expression of the cluster.^[4]^[7] Figure 1 shows a general depiction of the proposed biosynthesis. As a result of the two hydroxypropyl substituents and the two oxygen substituents of the acetal linker, the perylene core twists out of planarity. The natural product occurs as a single atropisomer.^[4]

Plant defense and susceptibility

To combat the onset of disease caused by Cercospora fungi, it has been proven that growing plants in lower light intensities can reduce the amount and severity of lesions caused by cercosporin.^[1]^[8] Some plant species use chitinases as a general defense mechanism to stop fungal infections.^[9] It has been observed that cercosporin-producing fungi that contain the Avr4 gene produce an effector that acts as a chitin-binding protein, allowing the fungi to be more virulent.^[9]

References

^ ^a ^b Daub ME, Herrero S, Chung KR (November 2005). "Photoactivated perylenequinone toxins in fungal pathogenesis of plants". FEMS Microbiology Letters. 252 (2): 197–206. doi:10.1016/j.femsle.2005.08.033. PMID 16165316.
^ Kuyama, Shimpei; Tamura, Teiichi (1957). "Cercosporin. A Pigment of Cercosporina Kikuchii Matsumoto et Tomoyasu. I. Cultivation of Fungus, Isolation and Purification of Pigment". J. Am. Chem. Soc. 79 (21): 5725–5726. doi:10.1021/ja01578a038.
^ Kuyama, Shimpei; Tamura, Teiichi (1957). "Cercosporin. A Pigment of Cercosporina Kikuchii Matsumoto et Tomoyasu. II. Physical and Chemical Properties of Cercosporin and its Derivatives". J. Am. Chem. Soc. 79 (21): 5726–5729. doi:10.1021/ja01578a039.
^ ^a ^b ^c ^d ^e ^f Newman AG, Townsend CA (March 2016). "Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae". Journal of the American Chemical Society. 138 (12): 4219–4228. doi:10.1021/jacs.6b00633. PMC 5129747. PMID 26938470.
^ Jenns AE, Daub ME, Upchurch RG (1989). "Regulation of Cercosporin Accumulation in Culture by Medium and Temperature Manipulation" (PDF). Phytopathology. 79 (2): 213–219. doi:10.1094/Phyto-79-213.
^ ^a ^b Choquer M, Dekkers KL, Chen HQ, Cao L, Ueng PP, Daub ME, Chung KR (May 2005). "The CTB1 gene encoding a fungal polyketide synthase is required for cercosporin biosynthesis and fungal virulence of Cercospora nicotianae". Molecular Plant-Microbe Interactions. 18 (5): 468–476. doi:10.1094/mpmi-18-0468. PMID 15915645.
^ Chen H, Lee MH, Daub ME, Chung KR (May 2007). "Molecular analysis of the cercosporin biosynthetic gene cluster in Cercospora nicotianae". Molecular Microbiology. 64 (3): 755–770. doi:10.1111/j.1365-2958.2007.05689.x. PMID 17462021. S2CID 40965980.
^ Calpouzos L, Stalknecht GF (1967). "Symptoms of Cercospora leaf spot of sugar beets influenced by light intensity". Phytopathology. 57: 799–800.
^ ^a ^b Santos Rezende J, Zivanovic M, Costa de Novaes MI, Chen ZY (January 2020). "The AVR4 effector is involved in cercosporin biosynthesis and likely affects the virulence of Cercospora cf. flagellaris on soybean". Molecular Plant Pathology. 21 (1): 53–65. doi:10.1111/mpp.12879. PMC 6913201. PMID 31642594.

[:0-1] Daub ME, Herrero S, Chung KR (November 2005). "Photoactivated perylenequinone toxins in fungal pathogenesis of plants". FEMS Microbiology Letters. 252 (2): 197–206. doi:10.1016/j.femsle.2005.08.033. PMID 16165316.

[2] Kuyama, Shimpei; Tamura, Teiichi (1957). "Cercosporin. A Pigment of Cercosporina Kikuchii Matsumoto et Tomoyasu. I. Cultivation of Fungus, Isolation and Purification of Pigment". J. Am. Chem. Soc. 79 (21): 5725–5726. doi:10.1021/ja01578a038.

[3] Kuyama, Shimpei; Tamura, Teiichi (1957). "Cercosporin. A Pigment of Cercosporina Kikuchii Matsumoto et Tomoyasu. II. Physical and Chemical Properties of Cercosporin and its Derivatives". J. Am. Chem. Soc. 79 (21): 5726–5729. doi:10.1021/ja01578a039.

[:1-4] ^ ^a ^b ^c ^d ^e ^f Newman AG, Townsend CA (March 2016). "Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae". Journal of the American Chemical Society. 138 (12): 4219–4228. doi:10.1021/jacs.6b00633. PMC 5129747. PMID 26938470.

[5] Jenns AE, Daub ME, Upchurch RG (1989). "Regulation of Cercosporin Accumulation in Culture by Medium and Temperature Manipulation" (PDF). Phytopathology. 79 (2): 213–219. doi:10.1094/Phyto-79-213.

[:2-6] Choquer M, Dekkers KL, Chen HQ, Cao L, Ueng PP, Daub ME, Chung KR (May 2005). "The CTB1 gene encoding a fungal polyketide synthase is required for cercosporin biosynthesis and fungal virulence of Cercospora nicotianae". Molecular Plant-Microbe Interactions. 18 (5): 468–476. doi:10.1094/mpmi-18-0468. PMID 15915645.

[7] Chen H, Lee MH, Daub ME, Chung KR (May 2007). "Molecular analysis of the cercosporin biosynthetic gene cluster in Cercospora nicotianae". Molecular Microbiology. 64 (3): 755–770. doi:10.1111/j.1365-2958.2007.05689.x. PMID 17462021. S2CID 40965980.

[8] Calpouzos L, Stalknecht GF (1967). "Symptoms of Cercospora leaf spot of sugar beets influenced by light intensity". Phytopathology. 57: 799–800.

[:3-9] Santos Rezende J, Zivanovic M, Costa de Novaes MI, Chen ZY (January 2020). "The AVR4 effector is involved in cercosporin biosynthesis and likely affects the virulence of Cercospora cf. flagellaris on soybean". Molecular Plant Pathology. 21 (1): 53–65. doi:10.1111/mpp.12879. PMC 6913201. PMID 31642594.

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