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

B. Franke, J. S. Mylne, K. J. Rosengren

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

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.

LanguageEnglish
Pages137-146
Number of pages10
JournalNatural Product Reports
Volume35
Issue number2
DOIs
Publication statusPublished - Feb 2018

Cite this

@article{4348d7fbc59240f3b7aec234cef85cc8,
title = "Buried treasure: biosynthesis, structures and applications of cyclic peptides hidden in seed storage albumins",
abstract = "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.",
keywords = "TRYPSIN-INHIBITOR SFTI-1, SERINE-PROTEASE INHIBITORS, ASPARAGINYL-ENDOPEPTIDASE, SUNFLOWER SEEDS, MATRIPTASE INHIBITORS, BACKBONE CYCLIZATION, PROTEINS, FAMILY, MACROCYCLIZATION, DESIGN",
author = "B. Franke and Mylne, {J. S.} and Rosengren, {K. J.}",
year = "2018",
month = "2",
doi = "10.1039/c7np00066a",
language = "English",
volume = "35",
pages = "137--146",
journal = "Natural Product Reports",
issn = "0265-0568",
publisher = "ROYAL SOC CHEMISTRY",
number = "2",

}

Buried treasure : biosynthesis, structures and applications of cyclic peptides hidden in seed storage albumins. / Franke, B.; Mylne, J. S.; Rosengren, K. J.

In: Natural Product Reports, Vol. 35, No. 2, 02.2018, p. 137-146.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Buried treasure

T2 - Natural Product Reports

AU - Franke, B.

AU - Mylne, J. S.

AU - Rosengren, K. J.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - TRYPSIN-INHIBITOR SFTI-1

KW - SERINE-PROTEASE INHIBITORS

KW - ASPARAGINYL-ENDOPEPTIDASE

KW - SUNFLOWER SEEDS

KW - MATRIPTASE INHIBITORS

KW - BACKBONE CYCLIZATION

KW - PROTEINS

KW - FAMILY

KW - MACROCYCLIZATION

KW - DESIGN

U2 - 10.1039/c7np00066a

DO - 10.1039/c7np00066a

M3 - Article

VL - 35

SP - 137

EP - 146

JO - Natural Product Reports

JF - Natural Product Reports

SN - 0265-0568

IS - 2

ER -