Authors
Sebastian Götze, Tanya Decker, Sven Balluff, Christine Beemelmanns
Published in
Natural product reports. Oct 15, 2026. Epub Oct 15, 2026.
Abstract
Covering: 1966 to 2026γ-Amino acids are structurally diverse non-proteinogenic building blocks that endow bacterial natural products with unique conformational, physicochemical, and biological properties. Although individual γ-amino acid-containing metabolites have been extensively investigated, their structural diversity, biosynthetic origins, and functional significance have rarely been considered from a unified perspective. Here, we review nearly six decades of research on bacterial γ-amino acid-containing natural products, covering from 1966 and the discovery of bleomycin to genome-guided discoveries in 2026. We discuss the major structural classes of γ-amino acids, including GABA-derived, β-keto, statine-type, vinylogous, fully reduced, and masked amino acid-derived motifs, and highlight how these building blocks are generated through primary metabolism, hybrid NRPS-PKS assembly lines, and specialized tailoring reactions. Particular emphasis is placed on the relationships between γ-amino acid structure, biosynthetic logic, and biological function, including their roles in protease inhibition, covalent target engagement, metallophore activity, and microbial ecology. Finally, we discuss emerging opportunities for genome mining and biosynthetic engineering that are expected to accelerate the discovery and exploitation of γ-amino acid-containing natural products.
PMID:
42876392
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.
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