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Updated: Sep 13, 2025
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Discovery and Characterization of Oxazolismycin, an Oxazole-Containing Natural Product with an Atypical Loading
Yuwei Pan1,2, Guangde Jiang2,3, Chunshuai Huang2
1Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.
Abstract:
Natural products (NPs) remain a vital source of bioactive molecules, with pyridine-containing compounds displaying diverse biological activities. This study presents the discovery of oxazolismycin, a novel pyridine-containing NP characterized by an oxazole-pyridine scaffold. Genome mining of Streptomyces griseochromogenes ATCC 14511 revealed a biosynthetic gene cluster encoding an NRPS-PKS assembly line homologous to those responsible for caerulomycin and collismycin biosynthesis. Gene knockouts and metabolite analysis of mutant strains unveiled the biosynthetic mechanism of oxazolismycin, including a previously uncharacterized β-ketoacyl-[acyl-carrier-protein] synthase III (KAS III), OxaC, which plays a noncanonical role in acyl group loading for NRPS initiation. Additionally, oxazolismycin exhibits notable angiotensin-converting enzyme (ACE) inhibition (IC50 = 0.326 ± 0.070 μM), suggesting its potential as a lead compound for ACE inhibitor development. These findings expand our understanding of pyridine-based NP biosynthesis, providing new insights into their enzymatic and structural diversity.
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