Cyr Anthony, Wilderman P Ross, Determan Mara, Peters Reuben J
Iowa State University, Department of Biochemistry, Biophysics, and Molecular Biology, Ames, Iowa 50011, USA.
J Am Chem Soc. 2007 May 30;129(21):6684-5. doi: 10.1021/ja071158n. Epub 2007 May 5.
Labdane-related diterpenoids are a large group of over 5,000 natural products whose biosynthesis typically proceeds through a labdadienyl/copalyl diphosphate (CPP) intermediate to a further cyclized and/or rearranged hydrocarbon diterpene en route to more elaborated compounds. Here we report a modular approach for facile biosynthesis of labdane-related diterpenes wherein base pGGxC vectors capable of introducing bacterial production of any one of the three common stereoisomers of CPP can be co-introduced with diterpene synthases that convert these CPP intermediates to specific diterpene hydrocarbon skeletal structures. The utility of this approach is demonstrated by individually engineering to produce any one of eight different diterpene skeletal structures, which collectively serve as precursors to literally thousands of distinct natural products.
半日花烷型二萜类化合物是一大类超过5000种的天然产物，其生物合成通常通过一个半日花二烯基/贝壳杉烯二磷酸酯（CPP）中间体，进一步环化和/或重排为烃类二萜，进而生成更复杂的化合物。在此，我们报道了一种用于简便生物合成半日花烷型二萜类化合物的模块化方法，其中能够引入细菌生产三种常见立体异构体中任何一种CPP的基础pGGxC载体，可以与将这些CPP中间体转化为特定二萜烃骨架结构的二萜合酶共同引入。通过单独设计以产生八种不同二萜骨架结构中的任何一种，证明了该方法的实用性，这些骨架结构共同作为数千种不同天然产物的前体。
