Identification of the Amipurimycin Gene Cluster Yields Insight into the Biosynthesis of C9 Sugar Nucleoside Antibiotics

Abstract

Feeding studies indicate a possible synthetic pattern for the N-terminal cis-aminocyclopentane carboxylic acid (ACPC) and suggest an unusual source of the highcarbon sugar skeleton of amipurimycin (APM). The biosynthetic gene cluster of APM was identified and confirmed by in vivo experiments. A C9 core intermediate was discovered from null mutants of ACPC pathway, and an ATP-grasp enzyme (ApmA8) was reconstituted in vitro for ACPC loading. Our observations allow a first proposal of the APM biosynthetic pathway. Letter pubs.acs.org/OrgLett

Anti-Foc RT4 Activity of a Newly Isolated Streptomyces sp. 5–10 From a Medicinal Plant (Curculigo capitulata)

“…211726 known as the production of antimicrobial azalomycin F3a (Xu et al, 2017). Cluster 15 showed 86% of similarity with PKS-T1 of Streptomyces novoguineensis responsible for producing antimicrobial amipurimycin (Kang et al, 2019). Cluster 27 had 83% of similarity with PKS-T1 from S. violaceusniger, which participated in the biosynthesis of antibacterial compounds such as nigericin (Harvey et al, 2007).…”

The Miharamycins and Amipurimycin: their Structural Revision and the Total Synthesis of the Latter

“…Thes tructures of miharamycins,r evised similarly to amipurimycin with the configurations at C3' and C8' being inverted, is finally confirmed by X-ray diffraction analysis of the authentic sample.T hese findings will support the characterization of the biosynthetic pathways for the formation of the miharamycins and amipurimycin, which has just become an area of interest. [9,20]…”

“…Herein, we report the final structural confirmation of amipurimycin and miharamycins. [9] Besides the necessary revision of the configuration at C3', acomparison of the NMR spectroscopy data of the synthetic amipurimycin (1a-d)a nd their 8'R antipodes (1e-h) [8] also led us to propose ar evision of the originally assigned S configuration at C8';t he H8' signals of 1a-d appear at d = 4.33-4.37 ppm, while those of the 8'R antipodes at d = 4.08-4.14 ppm are much closer to the reported d = 3.96 ppm for the natural amipurimycin. [10] Thesmaller Dd (À0.06 to 0.04 ppm) Figure 1.…”

The Miharamycins and Amipurimycin: their Structural Revision and the Total Synthesis of the Latter

“…The inversion of the originally proposed configuration of C3′ in miharamycins would lead to a conformationally restricted trans ‐fused dioxabicyclo[4.3.0]nonane sugar scaffold. Herein, we report the final structural confirmation of amipurimycin and miharamycins …”

“…The structures of miharamycins, revised similarly to amipurimycin with the configurations at C3′ and C8′ being inverted, is finally confirmed by X‐ray diffraction analysis of the authentic sample. These findings will support the characterization of the biosynthetic pathways for the formation of the miharamycins and amipurimycin, which has just become an area of interest …”