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. 2007 May 30;129(21):6684-5.
doi: 10.1021/ja071158n. Epub 2007 May 5.

A modular approach for facile biosynthesis of labdane-related diterpenes

Anthony Cyr  1 , P Ross Wilderman, Mara Determan, Reuben J Peters
Affiliations

A modular approach for facile biosynthesis of labdane-related diterpenes

Anthony Cyr et al. J Am Chem Soc. .

Abstract

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 E. coli to produce any one of eight different diterpene skeletal structures, which collectively serve as precursors to literally thousands of distinct natural products.

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Figures

Figure 1
Figure 1
Production of ent-kaur-16-ene (6) by E. coli transformed with pGGeC and pDEST15/rAtKS. Total ion chromatogram from GC-MS analysis of organic solvent eluant of Diaion HP-20 beads from a mixed phase culture (see Supporting Information).
Scheme 1
Scheme 1
Modular approach to labdane-related diterpene biosynthesis.
See this image and copyright information in PMC

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