Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

作者: Fang Yun Lim , Yanpeng Hou , Yiming Chen , Jee-Hwan Oh , Inhyung Lee

DOI: 10.1128/AEM.07710-11

关键词: Aspergillus fumigatusAnthraquinonesBiologySecondary metabolismGeneticsGene clusterThioesterasePolyketideGenePolyketide synthase

摘要: Endocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. Several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major has identified. Here we describe our and regulatory characterization the Aspergillus fumigatus. This first report species. The genes required production are regulated by global regulator metabolism, LaeA, encode an iterative nonreducing synthase (encA), physically discrete metallo-β-lactamase type thioesterase (encB), monooxygenase (encC). Interestingly, deletion immediately adjacent encC, termed encD encoding putative 2-oxoglutarate-Fe(II) oxidoreductase, resulted higher levels than wild-type strain, whereas overexpression eliminated accumulation. We found encA transcript encA-D endocrocin. discuss model enc one evolutionary origin fungal anthraquinones derived from metallo-β-lactamase-type thioesterase.

参考文章(47)
Mizuno D, Fujikawa F, Hirayama T, Otsuka M, Nishida N, Kasahara T, [Anti-tumor activities of some lichen products and their degradation products (author's transl)]. Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan. ,vol. 100, pp. 755- ,(1980) , 10.1248/YAKUSHI1947.100.7_755
Wolfgang Steglich, Wolfgang Reininger, A synthesis of endocrocin, endocrocin-9-anthrone, and related compounds Journal of the Chemical Society D: Chemical Communications. pp. 178a- ,(1970) , 10.1039/C2970000178A
Riikka Räisänen, Heikki Björk, Paavo H. Hynninen, Two-dimensional TLC separation and mass spectrometric identification of anthraquinones isolated from the fungus Dermocybe sanguinea. Zeitschrift für Naturforschung C. ,vol. 55, pp. 195- 202 ,(2000) , 10.1515/ZNC-2000-3-410
Sten Gatenbeck, Olle Snellman, Arne Magnéli, Georg Andersson, Einar Stenhagen, H. Palmstierna, The Occurrence of Endocrocin in Penicillium islandicum. Acta Chemica Scandinavica. ,vol. 13, pp. 386- 387 ,(1959) , 10.3891/ACTA.CHEM.SCAND.13-0386
Yanran Li, Yit-Heng Chooi, Yuewei Sheng, Joan S. Valentine, Yi Tang, Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an α-hydroxylation-dependent Claisen-like cyclization catalyzed by a dimanganese thioesterase. Journal of the American Chemical Society. ,vol. 133, pp. 15773- 15785 ,(2011) , 10.1021/JA206906D
Fetzner S., Oxygenases without requirement for cofactors or metal ions. Applied Microbiology and Biotechnology. ,vol. 60, pp. 243- 257 ,(2002) , 10.1007/S00253-002-1123-4
Robyn M Perrin, Natalie D Fedorova, Jin Woo Bok, Robert A Cramer Jr, Jennifer R Wortman, H Stanley Kim, William C Nierman, Nancy P Keller, None, Transcriptional Regulation of Chemical Diversity in Aspergillus fumigatus by LaeA PLOS Pathogens. ,vol. 3, pp. 508- 517 ,(2007) , 10.1371/JOURNAL.PPAT.0030050
Clay C. C. Wang, Yi-Ming Chiang, Po-Lin Kuo, Jiunn-Kae Chang, Ya-Ling Hsu, Norsolorinic acid from Aspergillus nidulans inhibits the proliferation of human breast adenocarcinoma MCF-7 cells via Fas-mediated pathway. Basic & Clinical Pharmacology & Toxicology. ,vol. 102, pp. 491- 497 ,(2008) , 10.1111/J.1742-7843.2008.00237.X
Naoya KIKUCHI, Mayumi TESHIBA, Takafumi TSUTSUMI, Ryosuke FUDOU, Hiromichi NAGASAWA, Shohei SAKUDA, Endocrocin and Its Derivatives from the Japanese Mealybug Planococcus kraunhiae Bioscience, Biotechnology, and Biochemistry. ,vol. 75, pp. 764- 767 ,(2011) , 10.1271/BBB.100742