在1942年,，從真菌中首次分離出一種稱為密擠青霉酸（stipitatic acid）的"不明"芳香化合物,，直到1945年才弄清楚其結(jié)構,，它的結(jié)構太絕無僅有了，以致引起了有機化學理解的一場革命,。
密擠青霉酸非常罕見,，因為它顯示出與六元環(huán)苯類化合物類似的芳香族特性，卻是一個稱為托酚酮的七元碳環(huán),。為了解托酚酮而發(fā)展的新理論模型,，現(xiàn)在鞏固了我們對有機化學中結(jié)構和鍵的了解。
但是,，真菌如何能在生物學條件下合成這樣一種產(chǎn)品直到現(xiàn)在還是個謎,。
研究人員結(jié)合遺傳學與化學方法，確定出負責此合成過程的基因,，并阻斷此合成通路的不同環(huán)節(jié),，以在分子水平闡明托酚酮結(jié)構的產(chǎn)生，該結(jié)構也是其他許多真菌化合物的母核,，它們包括密擠青霉酸,、抗抑郁藥xenovulenes和抗瘧藥軟毛青霉酸（puberulic acid）。
認識托酚酮生物合成通路不僅是一件有趣的事,，也可能導致新藥物的發(fā)現(xiàn),。（生物谷bioon.com）
doi:10.1073/pnas.1201469109
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PMID:
Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis
J. Davison, A. al Fahad, M. Cai, Z. Song, S. Y. Yehia, C. M. Lazarus, A. M. Bailey, T. J. Simpson, R. J. Cox
A gene cluster encoding the biosynthesis of the fungal tropolone stipitatic acid was discovered in Talaromyces stipitatus (Penicillium stipitatum) and investigated by targeted gene knockout. A minimum of three genes are required to form the tropolone nucleus: tropA encodes a nonreducing polyketide synthase which releases 3-methylorcinaldehyde; tropB encodes a FAD-dependent monooxygenase which dearomatizes 3-methylorcinaldehyde via hydroxylation at C-3; and tropC encodes a non-heme Fe(II)-dependent dioxygenase which catalyzes the oxidative ring expansion to the tropolone nucleus via hydroxylation of the 3-methyl group. The tropA gene was characterized by heterologous expression in Aspergillus oryzae, whereas tropB and tropC were successfully expressed in Escherichia coli and the purified TropB and TropC proteins converted 3-methylorcinaldehyde to a tropolone in vitro. Finally, knockout of the tropD gene, encoding a cytochrome P450 monooxygenase, indicated its place as the next gene in the pathway, probably responsible for hydroxylation of the 6-methyl group. Comparison of the T. stipitatus tropolone biosynthetic cluster with other known gene clusters allows clarification of important steps during the biosynthesis of other fungal compounds including the xenovulenes, citrinin, sepedonin, sclerotiorin, and asperfuranone.
