A Modular Approach for Facile Biosynthesis of Labdane-Related Diterpenes

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• 作者：Anthony Cyr ; P. Ross Wilderman ; Mara Determan ; Reuben J. Peters
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：May 30, 2007
• 年：2007
• 卷：129
• 期：21
• 页码：6684 - 6685
• 全文大小：46K
• 年卷期：v.129,no.21(May 30, 2007)
• ISSN：1520-5126

文摘

Labdane-related diterpenoids are a large group of over 5000 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 E. coli to produce any one of eight different diterpene skeletal structures, which collectively serve as precursors to literally thousands of distinct natural products.