Terpene biosynthesis: Modularity rules

Eric Oldfield, Fu Yang Lin

Research output: Contribution to journalReview articlepeer-review

Abstract

Terpenes are the largest class of small-molecule natural products on earth, and the most abundant by mass. Here, we summarize recent developments in elucidating the structure and function of the proteins involved in their biosynthesis. There are six main building blocks or modules (α, β, γ, δ, ε, and ζ) that make up the structures of these enzymes: the αα and αδ head-to-tail trans-prenyl transferases that produce trans-isoprenoid diphosphates from C 5 precursors; the ε head-to-head prenyl transferases that convert these diphosphates into the tri- and tetraterpene precursors of sterols, hopanoids, and carotenoids; the βγ di- and triterpene synthases; the ζ head-to-tail cis-prenyl transferases that produce the cis-isoprenoid diphosphates involved in bacterial cell wall biosynthesis; and finally the α, αβ, and αβγ terpene synthases that produce plant terpenes, with many of these modular enzymes having originated from ancestral α and β domain proteins. We also review progress in determining the structure and function of the two 4Fe-4S reductases involved in formation of the C 5 diphosphates in many bacteria, where again, highly modular structures are found. Natural building blocks: Recent progress has been achieved in determining the structure, function, and inhibition of the enzymes responsible for the formation of terpenes and isoprenoids. Most of these enzymes contain combinations of α-, β-, γ-, δ-, ε-, and/or ζ-domain structures that in many cases are fused to form modular proteins. Gene fusion, exon loss, and recombination are thought to play major roles in the genesis of these enzymes.

Original languageEnglish (US)
Pages (from-to)1124-1137
Number of pages14
JournalAngewandte Chemie - International Edition
Volume51
Issue number5
DOIs
StatePublished - Jan 27 2012

Keywords

  • biosynthesis
  • evolution
  • isoprenoids
  • metalloproteins
  • terpenes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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