Directing Biosynthesis: Practical Supply of Natural and Unnatural Cyanobactins

Methods Enzymol. 2016:575:1-20. doi: 10.1016/bs.mie.2016.02.012. Epub 2016 Mar 16.

Abstract

The increasingly rapid accumulation of genomic information is revolutionizing natural products discovery. However, the translation of sequence data to chemical products remains a challenge. Here, we detail methods used to circumvent the supply problem of cyanobactin natural products, both by engineered synthesis in Escherichia coli and by using purified enzymes in vitro. Such methodologies exploit nature's strategies of combinatorial chemistry in the cyanobactin class of RiPP natural products. As a result, it is possible to synthesize a wide variety of natural and unnatural compounds.

Keywords: Diversity-generating metabolism; Marine natural products; Metabolic engineering; Ribosomally synthesized and posttranslationally modified peptide; Secondary metabolism.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Biosynthetic Pathways*
  • Cyanobacteria / chemistry
  • Cyanobacteria / genetics
  • Cyanobacteria / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Genes, Bacterial
  • Metabolic Engineering / methods*
  • Multigene Family
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / genetics
  • Peptides, Cyclic / metabolism*
  • Protein Processing, Post-Translational
  • Ribosomes / genetics
  • Ribosomes / metabolism

Substances

  • Bacterial Proteins
  • Biological Products
  • Peptides, Cyclic