Cercosporin

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Cercosporin
Cercosporin.png
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
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
PubChem CID
UNII
  • 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
  • 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
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).

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]

Contents

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]

Figure 1: Proposed biosynthesis of cercosporin Cercosporin biosynthesis.gif
Figure 1: Proposed biosynthesis of cercosporin

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]

Related Research Articles

<span class="mw-page-title-main">Secondary metabolite</span> Type of organic compound

Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the normal growth, development, or reproduction of the organism. Instead, they generally mediate ecological interactions, which may produce a selective advantage for the organism by increasing its survivability or fecundity. Specific secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defense against herbivory and other interspecies defenses. Humans use secondary metabolites as medicines, flavourings, pigments, and recreational drugs.

Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity.

Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms. While there exist a wide range of peptides that are not synthesized by ribosomes, the term nonribosomal peptide typically refers to a very specific set of these as discussed in this article.

<span class="mw-page-title-main">Flavin adenine dinucleotide</span> Redox-active coenzyme

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex.

<span class="mw-page-title-main">Flavoprotein</span> Protein family

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. The flavoproteins are some of the most-studied families of enzymes.

Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.

<i>Cercospora beticola</i> Species of fungus

Cercospora beticola is a fungal plant pathogen which typically infects plants of the genus Beta, within the family of Chenopodiaceae. It is the cause of Cercospora leaf spot disease in sugar beets, spinach and swiss chard. Of these hosts, Cercospora leaf spot is the most economically impactful in sugar beets. Cercospora beticola is a deuteromycete fungus that reproduces using conidia. There is no teleomorph stage. C. beticola is a necrotrophic fungus that uses phytotoxins specifically Cercospora beticola toxin (CBT) to kill infected plants. CBT causes the leaf spot symptom and prevents root formation. Yield losses from Cercospora leaf spot are around 20 percent.

<i>Cercospora melongenae</i> Fungal disease of eggplant leaves

Cercospora melongenae is a fungal plant pathogen that causes leaf spot on eggplant. It is a deuteromycete fungus that is primarily confined to eggplant species. Some other host species are Solanum aethiopicum and Solanum incanum. This plant pathogen only attacks leaves of eggplants and not the fruit. It is fairly common among the fungi that infect community gardens and home gardens of eggplant. Generally speaking, Cercospora melongenae attacks all local varieties of eggplants, but is most severe on the Philippine eggplant and less parasitic on a Siamese variety.

<span class="mw-page-title-main">Fungus</span> Biological kingdom, separate from plants and animals

A fungus is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from the other eukaryotic kingdoms, which, by one traditional classification, includes Plantae, Animalia, Protozoa, and Chromista.

Chaetomium cupreum is a fungus in the family Chaetomiaceae. It is able to decay in manufactured cellulosic materials, and is known to antagonize a wide range of soil microorganisms. This species is component of the biocontrol agent, Ketomium, a commercial biofungicide. It has also been investigated for use in the production of natural dyes. Chaetomium cupreum is mesophilic and known to occur in harsh environments and can rapidly colonize organic substrates in soil. Laboratory cultures of C. cupreum can be propagated on a range of common growth media including potato dextrose at ambient or higher than ambient temperature producing cottony white colonies with a reddish reverse.

<i>Penicillium chrysogenum</i> Species of fungus

Penicillium chrysogenum is a species of fungus in the genus Penicillium. It is common in temperate and subtropical regions and can be found on salted food products, but it is mostly found in indoor environments, especially in damp or water-damaged buildings. It has been recognised as a species complex that includes P. notatum, P. meleagrinum, and P. cyaneofulvum. Molecular phylogeny has established that Alexander Fleming's first discovered penicillin producing strain is of a distinct species, P. rubens, and not of P. notatum. It has rarely been reported as a cause of human disease. It is the source of several β-lactam antibiotics, most significantly penicillin. Other secondary metabolites of P. chrysogenum include roquefortine C, meleagrin, chrysogine, 6-MSA YWA1/melanin, andrastatin A, fungisporin, secalonic acids, sorbicillin, and PR-toxin.

<span class="mw-page-title-main">Corn grey leaf spot</span> Fungal disease of maize

Grey leaf spot (GLS) is a foliar fungal disease that affects maize, also known as corn. GLS is considered one of the most significant yield-limiting diseases of corn worldwide. There are two fungal pathogens that cause GLS: Cercospora zeae-maydis and Cercospora zeina. Symptoms seen on corn include leaf lesions, discoloration (chlorosis), and foliar blight. Distinct symptoms of GLS are rectangular, brown to gray necrotic lesions that run parallel to the leaf, spanning the spaces between the secondary leaf veins. The fungus survives in the debris of topsoil and infects healthy crops via asexual spores called conidia. Environmental conditions that best suit infection and growth include moist, humid, and warm climates. Poor airflow, low sunlight, overcrowding, improper soil nutrient and irrigation management, and poor soil drainage can all contribute to the propagation of the disease. Management techniques include crop resistance, crop rotation, residue management, use of fungicides, and weed control. The purpose of disease management is to prevent the amount of secondary disease cycles as well as to protect leaf area from damage prior to grain formation. Corn grey leaf spot is an important disease of corn production in the United States, economically significant throughout the Midwest and Mid-Atlantic regions. However, it is also prevalent in Africa, Central America, China, Europe, India, Mexico, the Philippines, northern South America, and Southeast Asia. The teleomorph of Cercospora zeae-maydis is assumed to be Mycosphaerella sp.

Phenolic lipids are a class of natural products composed of long aliphatic chains and phenolic rings. Phenolic lipids occur in plants, fungi and bacteria.

White Collar-1 (wc-1) is a gene in Neurospora crassa encoding the protein WC-1. WC-1 has two separate roles in the cell. First, it is the primary photoreceptor for Neurospora and the founding member of the class of principle blue light photoreceptors in all of the fungi. Second, it is necessary for regulating circadian rhythms in FRQ. It is a key component of a circadian molecular pathway that regulates many behavioral activities, including conidiation. WC-1 and WC-2, an interacting partner of WC-1, comprise the White Collar Complex (WCC) that is involved in the Neurospora circadian clock. WCC is a complex of nuclear transcription factor proteins, and contains transcriptional activation domains, PAS domains, and zinc finger DNA-binding domains (GATA). WC-1 and WC-2 heterodimerize through their PAS domains to form the White Collar Complex (WCC).

<span class="mw-page-title-main">Gephyronic acid</span> Chemical compound

Gephyronic acid is a polyketide that exists as an equilibrating mixture of structural isomers. In nature, gephyronic acid is produced by slow growing myxobacterium: Archangium gephyra strain Ar3895 and Cystobacter violaceus strain Cb vi76. It is the first antibiotic in myxobacteria that was reported to specifically inhibit eukaryotic protein synthesis.

<span class="mw-page-title-main">Lolitrem B</span> Chemical compound

Lolitrem B is one of many toxins produced by a fungus called Epichloë festucae var. lolii), which grows in Lolium perenne. The fungus is symbiotic with the ryegrass; it doesn't harm the plant, and the toxins it produces kill insects that feed on ryegrass. Lolitrem B is one of these toxins, but it is also harmful to mammals. The shoots and flowers of infected ryegrass have especially high concentrations of lolitrem B, and when livestock eat too much of them, they get perennial ryegrass staggers. At low doses the animals have tremors, and at higher doses they stagger, and at higher yet doses the animals become paralyzed and die. The blood pressure of the animals also goes up. The effect of the lolitrem B comes on slowly and fades out slowly, as it is stored in fat after the ryegrass is eaten. The condition is especially common in New Zealand and Australia, and plant breeders there have been trying to develop strains of fungus that produce toxins only harmful to pests, and not to mammals.

<i>BY1</i> Species of fungus

BY1 is a taxonomically unidentified basidiomycete fungus. ITS sequencing has placed it in the Russulales and is referred to as a stereaceous basidiomycete. Chemotaxonomically supporting its placement in this group, it produces fomannoxins and vibralactones. The fungus' mycelia were isolated from dead aspen in Minnesota, USA. It is presumed to decompose wood by white rot.

Metabolic gene clusters or biosynthetic gene clusters are tightly linked sets of mostly non-homologous genes participating in a common, discrete metabolic pathway. The genes are in physical vicinity to each other on the genome, and their expression is often coregulated. Metabolic gene clusters are common features of bacterial and most fungal genomes, and are less often found in other organisms. They are most widely known for producing secondary metabolites, which are the source or basis of most pharmaceutical compounds, natural toxins, and chemical communication and chemical warfare between organisms. Metabolic gene clusters are also involved in nutrient acquisition, toxin degradation, antimicrobial resistance, and vitamin biosynthesis. Given all these properties of metabolic gene clusters, they play a key role in shaping microbial ecosystems, including microbiome-host interactions. Thus several computational genomics tools have been developed to predict metabolic gene clusters.

<span class="mw-page-title-main">Dihydromaltophilin</span> Chemical compound

Dihydromaltophilin, or heat stable anti-fungal factor (HSAF), is a secondary metabolite of Streptomyces sp. and Lysobacter enzymogenes. HSAF is a polycyclic tetramate lactam containing a single tetramic acid unit and a 5,5,6-tricyclic system. HSAF has been shown to have anti-fungal activity mediated through the disruption of the biosynthesis of Sphingolipid's by targeting a ceramide synthase unique to fungi.

<span class="mw-page-title-main">Phoslactomycin B</span> Chemical compound

Phoslactomycin (PLM) is a natural product from the isolation of Streptomyces species. This is an inhibitor of the protein serine/threonine phosphatase which is the protein phosphate 2A (PP2A). The PP2A involves the growth factor of the cell such as to induce the formation of mitogen-activated protein interaction and playing a role in cell division and signal transduction. Therefore, PLM is used for the drug that prevents the tumor, cancer, or bacteria. There are nowsaday has 7 kinds of different PLM from PLM A to PLM G which differ the post-synthesis from the biosynthesis of PLM.

References

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  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.
  4. 1 2 3 4 5 6 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.
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  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.
  9. 1 2 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.