Biosynthesis and chemical diversity of β-lactone natural products

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

Research output: Contribution to journalReview article

3 Citations (Scopus)

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 1 2019

Fingerprint

Biosynthesis
Lactones
Biological Products
Cyclization
Fungi
Bacteria
Genes
Peptide Synthases
Porifera
Taxonomies
Ligases
Multigene Family
Bioactivity
Scaffolds
Pharmaceutical Preparations
Insects
Adenosine Triphosphate
Cells
Genome
Cell Line

PubMed: MeSH publication types

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

Cite this

Biosynthesis and chemical diversity of β-lactone natural products. / Robinson, Serina L.; Christenson, James K; Wackett, Lawrence P.

In: Natural Product Reports, Vol. 36, No. 3, 01.03.2019, p. 458-475.

Research output: Contribution to journalReview article

Robinson, Serina L. ; Christenson, James K ; Wackett, Lawrence P. / Biosynthesis and chemical diversity of β-lactone natural products. In: Natural Product Reports. 2019 ; Vol. 36, No. 3. pp. 458-475.
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