Biosynthesis of a Tricyclo[6.2.2.02,7]dodecane System by a Berberine Bridge Enzyme-Like Aldolase |
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Authors: | Hang Li Jinyu Hu Haochen Wei Dr Peter S Solomon Dr Keith A Stubbs Dr Yit-Heng Chooi |
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Institution: | 1. School of Molecular Sciences, The University of Western Australia, Perth, WA, 6009 Australia;2. Division of Plant Science, Research School of Biology, The Australian National University, Canberra, ACT, 2601 Australia |
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Abstract: | The aldol reaction is one of the most fundamental stereocontrolled carbon–carbon bond-forming reactions and is mainly catalyzed by aldolases in nature. Despite the fact that the aldol reaction has been widely proposed to be involved in fungal secondary metabolite biosynthesis, a dedicated aldolase that catalyzes stereoselective aldol reactions has only rarely been reported in fungi. Herein, we activated a cryptic polyketide biosynthetic gene cluster that was upregulated in the fungal wheat pathogen Parastagonospora nodorum during plant infection; this resulted in the production of the phytotoxic stemphyloxin II ( 1 ). Through heterologous reconstruction of the biosynthetic pathway and in vitro assay by using cell-free lysate from Aspergillus nidulans, we demonstrated that a berberine bridge enzyme (BBE)-like protein SthB catalyzes an intramolecular aldol reaction to establish the bridged tricyclo6.2.2.02,7]dodecane skeleton in the post-assembly tailoring step. The characterization of SthB as an aldolase enriches the catalytic toolbox of classic reactions and the functional diversities of the BBE superfamily of enzymes. |
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Keywords: | aldol reactions aldolases berberine bridge enzyme biosynthesis fungal polyketide |
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