8cg6

Structural highlights

Function

CTB1_CERNC Polyketide synthase; part of the gene cluster that mediates the biosynthesis of cercosporin, a light-activated, non-host-selective toxin (PubMed:12937958, PubMed:15915645, PubMed:26938470, PubMed:29610486). The perylenequinone chromophore of cercosporin absorbs light energy to attain an electronically-activated triplet state and produces active oxygen species such as the hydroxyl radical, superoxide, hydrogen peroxide or singlet oxygen upon reaction with oxygen molecules (PubMed:11701851). These reactive oxygen species cause damage to various cellular components including lipids, proteins and nucleic acids (PubMed:11701851). The first step of cercosporin biosynthesis is performed by the polyketide synthase CTB1 which catalyzes the formation of nor-toralactone (PubMed:23108075, PubMed:26938470, PubMed:29610486). The starter unit acyltransferase (SAT) domain of CTB1 initiates polyketide extension by the selective utilization of acetyl-CoA, which is elongated to the heptaketide in the beta-ketoacyl synthase (KS) domain by successive condensations with six malonyl units introduced by the malonyl acyltransferase (MAT) domain. The product template (PT) domain catalyzes C4-C9 and C2-C11 aldol cyclizations and dehydrations to a trihydroxynaphthalene, which is thought to be delivered to the thioesterase (TE) domain for product release (PubMed:23108075, PubMed:29610486). The bifunctional enzyme CTB3 then methylates nor-toralactone to toralactone before conducting an unusual oxidative aromatic ring opening (PubMed:17074519, PubMed:26938470). The O-methyltransferase CTB2 further methylates the nascent OH-6 of the CBT3 product, blocking further oxidation at this site before the reductase CTB6 reduces the 2-oxopropyl ketone at position C7, giving naphthalene (PubMed:17660442, PubMed:26938470). The FAD-dependent monooxygenase CTB5 in concert with the multicopper oxidase CTB12 are responsible for homodimerization of naphthalene with CTB7 installing the dioxepine moiety, finally producing cercosporin (PubMed:17660442, PubMed:30809363, PubMed:26938470). The fasciclin domain-containing protein CTB11 might act with CTB5 and CTB12 whereas the roles of CTB9 and CTB10 have still to be elucidated (By similarity).[UniProtKB:Q0UHZ9]^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

References

1. ↑ Chung KR, Ehrenshaft M, Wetzel DK, Daub ME. Cercosporin-deficient mutants by plasmid tagging in the asexual fungus Cercospora nicotianae. Mol Genet Genomics. 2003 Nov;270(2):103-13. PMID:12937958 doi:10.1007/s00438-003-0902-7
2. ↑ Choquer M, Dekkers KL, Chen HQ, Cao L, Ueng PP, Daub ME, Chung KR. The CTB1 gene encoding a fungal polyketide synthase is required for cercosporin biosynthesis and fungal virulence of Cercospora nicotianae. Mol Plant Microbe Interact. 2005 May;18(5):468-76. PMID:15915645 doi:10.1094/MPMI-18-0468
3. ↑ Dekkers KL, You BJ, Gowda VS, Liao HL, Lee MH, Bau HJ, Ueng PP, Chung KR. The Cercospora nicotianae gene encoding dual O-methyltransferase and FAD-dependent monooxygenase domains mediates cercosporin toxin biosynthesis. Fungal Genet Biol. 2007 May;44(5):444-54. PMID:17074519 doi:10.1016/j.fgb.2006.08.005
4. ↑ Chen HQ, Lee MH, Chung KR. Functional characterization of three genes encoding putative oxidoreductases required for cercosporin toxin biosynthesis in the fungus Cercospora nicotianae. Microbiology (Reading). 2007 Aug;153(Pt 8):2781-2790. PMID:17660442 doi:10.1099/mic.0.2007/007294-0
5. ↑ Newman AG, Vagstad AL, Belecki K, Scheerer JR, Townsend CA. Analysis of the cercosporin polyketide synthase CTB1 reveals a new fungal thioesterase function. Chem Commun (Camb). 2012 Dec 14;48(96):11772-4. PMID:23108075 doi:10.1039/c2cc36010a
6. ↑ Newman AG, Townsend CA. Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae. J Am Chem Soc. 2016 Mar 30;138(12):4219-28. PMID:26938470 doi:10.1021/jacs.6b00633
7. ↑ Herbst DA, Huitt-Roehl CR, Jakob RP, Kravetz JM, Storm PA, Alley JR, Townsend CA, Maier T. The structural organization of substrate loading in iterative polyketide synthases. Nat Chem Biol. 2018 Apr 2. pii: 10.1038/s41589-018-0026-3. doi:, 10.1038/s41589-018-0026-3. PMID:29610486 doi:http://dx.doi.org/10.1038/s41589-018-0026-3
8. ↑ Hu J, Sarrami F, Li H, Zhang G, Stubbs KA, Lacey E, Stewart SG, Karton A, Piggott AM, Chooi YH. Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system. Chem Sci. 2018 Nov 22;10(5):1457-1465. PMID:30809363 doi:10.1039/c8sc02870b
9. ↑ Daub ME, Ehrenshaft M. The Photoactivated Cercospora Toxin Cercosporin: Contributions to Plant Disease and Fundamental Biology. Annu Rev Phytopathol. 2000 Sep;38:461-490. PMID:11701851 doi:10.1146/annurev.phyto.38.1.461