Biosynthesis and chemical diversity of β-lactone natural products

Serina L. Robinson, James K. Christenson, Lawrence P. Wackett

Research output: Contribution to journalReview articlepeer-review

68 Scopus citations

Abstract

Covering: up to 2018 β-Lactones are strained rings that are useful organic synthons and pharmaceutical warheads. Over 30 core scaffolds of β-lactone natural products have been described to date, many with potent bioactivity against bacteria, fungi, or human cancer cell lines. β-Lactone natural products are chemically diverse and have high clinical potential, but production of derivatized drug leads has been largely restricted to chemical synthesis partly due to gaps in biochemical knowledge about β-lactone biosynthesis. Here we review recent discoveries in enzymatic β-lactone ring closure via ATP-dependent synthetases, intramolecular cyclization from seven-membered rings, and thioesterase-mediated cyclization during release from nonribosomal peptide synthetase assembly lines. We also comprehensively cover the diversity and taxonomy of source organisms for β-lactone natural products including their isolation from bacteria, fungi, plants, insects, and marine sponges. This work identifies computational and experimental bottlenecks and highlights future directions for genome-based discovery of biosynthetic gene clusters that may produce novel compounds with β-lactone rings.

Original languageEnglish (US)
Pages (from-to)458-475
Number of pages18
JournalNatural Product Reports
Volume36
Issue number3
DOIs
StatePublished - Mar 2019

Bibliographical note

Funding Information:
S. L. R. is supported by the National Science Foundation (NSF) Graduate Research Fellowship (Grant no. 00039202). J. K. C. acknowledges support from a Minnesota’s Discovery Research and InnoVation Economy (MnDRIVE) grant. We acknowledge insightful comments on the manuscript from Courtney C. Aldrich, Michael F. Freeman, and Erin E. Carlson.

Publisher Copyright:
© 2019 The Royal Society of Chemistry.

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