Natural product biosynthetic pathways have been studied experimentally for more than 60 years. During this period the basic biological building blocks for the major classes of natural products, including, terpenes, polyketides, nonribosomal peptides, and alkaloids, have been established and the outlines of the major pathways for their assembly have been elucidated. The investigation of natural product biosynthesis has evolved from a largely indirect science, in which the broad outlines of entire pathways had to be inferred from the results of precursor � product incorporation experiments, to a vibrant branch of mechanistic enzymology allowing the discovery of entirely new biochemical transformations and the detailed elucidation of their mechanisms and the protein structural basis for their mode of action. The modern era of genome mining has opened up the opportunity for the detailed dissection of entire biosynthetic pathways, and for the discovery of entirely new, even previously cryptic metabolites, as well as the exploitation of the biosynthetic reaction toolkit to synthetic biology. Current investigations are now revealing the evolution, programming, and regulation of complex biosynthetic transformations.

Award Address  (Alfred Bader Award in Bioinorganic or Bioorganic Chemistry sponsored by Alfred R. Bader Fund). Natural product biosynthesis: Where have we been, what have we learned, and where are we going?

245th National Meeting (2013)

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