Structural highlightsFunctionAUSE_EMENI Dioxygenase; part of the gene cluster B that mediates the biosynthesis of austinol and dehydroaustinol, two fungal meroterpenoids (PubMed:22329759). The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:22329759). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (PubMed:22329759). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (PubMed:22329759, PubMed:23865690). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (PubMed:22329759). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (PubMed:22329759). Finally, the cytochrome P450 monooxygenase ausG modifies austinolide to austinol (PubMed:22329759). Austinol can be further modified to dehydroaustinol which forms a diffusible complex with diorcinol that initiates conidiation (PubMed:22234162, PubMed:22329759). AusE catalyzes various oxidation reactions in addition to spiro-ring formation and works iteratively in the biosynthetic process to produce shunt products such as 5-hydroxyberkeleyone, preaustinoid C and austinoid C (PubMed:23865690).[1] [2] [3]
See AlsoReferences
- ↑ Rodriguez-Urra AB, Jimenez C, Nieto MI, Rodriguez J, Hayashi H, Ugalde U. Signaling the induction of sporulation involves the interaction of two secondary metabolites in Aspergillus nidulans. ACS Chem Biol. 2012 Mar 16;7(3):599-606. doi: 10.1021/cb200455u. Epub 2012 Jan, 24. PMID:22234162 doi:http://dx.doi.org/10.1021/cb200455u
- ↑ Lo HC, Entwistle R, Guo CJ, Ahuja M, Szewczyk E, Hung JH, Chiang YM, Oakley BR, Wang CC. Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans. J Am Chem Soc. 2012 Mar 14;134(10):4709-20. doi: 10.1021/ja209809t. Epub 2012 Feb, 29. PMID:22329759 doi:http://dx.doi.org/10.1021/ja209809t
- ↑ Matsuda Y, Awakawa T, Wakimoto T, Abe I. Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis. J Am Chem Soc. 2013 Jul 31;135(30):10962-5. doi: 10.1021/ja405518u. Epub 2013 Jul, 22. PMID:23865690 doi:http://dx.doi.org/10.1021/ja405518u
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