在1942年，从真菌中首次分离出一种称为密挤青霉酸（stipitatic acid）的"不明"芳香化合物，直到1945年才弄清楚其结构，它的结构太绝无仅有了，以致引起了有机化学理解的一场革命。
密挤青霉酸非常罕见，因为它显示出与六元环苯类化合物类似的芳香族特性，却是一个称为托酚酮的七元碳环。为了解托酚酮而发展的新理论模型，现在巩固了我们对有机化学中结构和键的了解。
但是，真菌如何能在生物学条件下合成这样一种产品直到现在还是个谜。
研究人员结合遗传学与化学方法，确定出负责此合成过程的基因，并阻断此合成通路的不同环节，以在分子水平阐明托酚酮结构的产生，该结构也是其他许多真菌化合物的母核，它们包括密挤青霉酸、抗抑郁药xenovulenes和抗疟药软毛青霉酸（puberulic acid）。
认识托酚酮生物合成通路不仅是一件有趣的事，也可能导致新药物的发现。（生物谷bioon.com）
doi:10.1073/pnas.1201469109
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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.
