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 language | English (US) |
|---|---|
| Pages (from-to) | 458-475 |
| Number of pages | 18 |
| Journal | Natural Product Reports |
| Volume | 36 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2019 |
Fingerprint
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 journal › Review article
}
TY - JOUR
T1 - Biosynthesis and chemical diversity of β-lactone natural products
AU - Robinson, Serina L.
AU - Christenson, James K
AU - Wackett, Lawrence P
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85063253174&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063253174&partnerID=8YFLogxK
U2 - 10.1039/c8np00052b
DO - 10.1039/c8np00052b
M3 - Review article
VL - 36
SP - 458
EP - 475
JO - Natural Product Reports
JF - Natural Product Reports
SN - 0265-0568
IS - 3
ER -