Buried treasure: biosynthesis, structures and applications of cyclic peptides hidden in seed storage albumins

Nat Prod Rep. 2018 Feb 21;35(2):137-146. doi: 10.1039/c7np00066a.


Covering: 1999 up to the end of 2017The small cyclic peptide SunFlower Trypsin Inhibitor-1 (SFTI-1) from sunflower seeds is the prototypic member of a novel family of natural products. The biosynthesis of these peptides is intriguing as their gene-encoded peptide backbone emerges from a precursor protein that also contains a seed storage albumin. The peptide sequence is cleaved out from the precursor and cyclised by the albumin-maturing enzymatic machinery. Three-dimensional solution NMR structures of a number of these peptides, and of the intact precursor protein preproalbumin with SFTI-1, have now been elucidated. Furthermore, the evolution of the family has been described and a detailed understanding of the biosynthetic steps, which are necessary to produce cyclic SFTI-1, is emerging. Macrocyclisation provides peptide stability and thus represents a key strategy in peptide drug development. Consequently the constrained structure of SFTI-1 has been explored as a template for protein engineering, for tuning selectivity towards clinically relevant proteases and for grafting in sequences with completely novel functions. Here we review the discovery of the SFTI-1 peptide family, their evolution, biosynthetic origin, and structural features, as well as highlight the potential applications of this unique class of natural products.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Albumins / chemistry
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Drug Design
  • Evolution, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / biosynthesis*
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology
  • Protein Engineering / methods
  • Seed Storage Proteins / biosynthesis
  • Seed Storage Proteins / chemistry*
  • Seed Storage Proteins / genetics
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology


  • Albumins
  • Anti-Infective Agents
  • Peptides, Cyclic
  • SFTI-1 peptide, sunflower
  • Seed Storage Proteins
  • Serine Proteinase Inhibitors