Enzymatic Formation of Unnatural Novel Chalcone, Stilbene, and Benzophenone Scaffolds by Plant Type III Polyketide Synthase

Enzymatic Formation of Unnatural Novel Chalcone, Stilbene, and Benzophenone Scaffolds by Plant Type III Polyketide Synthase
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DOI:
10.1021/ol802606w
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发表时间:
2009-02-05
期刊:
影响因子:
5.2
通讯作者:
Abe, Ikuro
Abe, Ikuro
中科院分区:
化学1区
文献类型:
--
作者:
Shi, She-Po;Wanibuchi, Kiyofumi;Abe, Ikuro

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利用木立芦荟(Aloe arborescens)八酮合成酶(OKS)合成了C-19六酮芪和C-21七酮查尔酮。值得注意的是,C21查耳酮形成活性在结构导向的OKS N222 G突变体中显著增加,该突变体从10个丙二酰辅酶A分子产生C-20十酮SEK 15。研究结果表明,进一步的战略,生产非天然聚酮化合物相结合的催化剂导向的生物合成和结构导向的工程III型PKS。
A C-19 hexaketide stilbene and a C-21 heptaketide chalcone were synthesized by Aloe arborescens octaketide synthase (OKS), a plant-specific type III polyketide synthase (PKS). Remarkably, the C21 chalcone-forming activity was dramatically increased in a structure-guided OKS N222G mutant that produces a C-20 decaketide SEK15 from 10 molecules of malonyl-CoA. The findings suggested further strategies for production of unnatural polyketides by combination of the precursor-directed biosynthesis and the structure-guided engineering of type III PKS.