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

作者：Franke, B.; Mylne, J. S.; Rosengren, K. J.^*

来源：Natural Product Reports, 2018, 35(2): 137-146.

DOI：10.1039/c7np00066a

• TRYPSIN-INHIBITOR SFTI-1
• SERINE-PROTEASE INHIBITORS
• ASPARAGINYL-ENDOPEPTIDASE
• SUNFLOWER SEEDS
• MATRIPTASE INHIBITORS
• BACKBONE CYCLIZATION
• PROTEINS
• FAMILY
• MACROCYCLIZATION
• DESIGN

The 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.

• 出版日期2018-2