A modular approach for facile biosynthesis of labdane-related diterpenes

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / metabolism*
  • Diterpenes / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Farnesyltranstransferase / metabolism
  • Plant Proteins / metabolism*
  • Polyisoprenyl Phosphates / biosynthesis
  • Stereoisomerism
  • Transformation, Genetic


  • Diterpenes
  • Plant Proteins
  • Polyisoprenyl Phosphates
  • Alkyl and Aryl Transferases
  • ent-kaurene synthetase A
  • Farnesyltranstransferase
  • geranylgeranyl pyrophosphate