Journal
ORGANIC CHEMISTRY FRONTIERS
Volume 9, Issue 2, Pages 462-470Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1qo01480c
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- Novo Nordisk Foundation, Denmark [NNF20CC0035580, NNF16OC0021746]
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Two new and highly complex macrolactones, Gargantulides B and C, were isolated from Amycolatopsis sp. strain CA-230715 during an antibacterial screening campaign. Genome sequencing revealed a large 216 kbp biosynthetic gene cluster and proposed a previously unreported biosynthetic pathway for Gargantulides A-C. The absolute configurations of Gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis.
Gargantulides B and C, two new and highly complex 52-membered glycosylated macrolactones, were isolated from Amycolatopsis sp. strain CA-230715 during an antibacterial screening campaign. The structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A, although containing additional beta-glucopyranose and/or alpha-arabinofuranose monosaccharides separately attached to their backbones. Genome sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster, among the largest type I PKS clusters described so far, and the proposal of a previously unreported biosynthetic pathway for gargantulides A-C. The absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type I PKS. In addition, the absolute stereochemistry of gargantulide A has now been revised and completed. Gargantulides B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii.
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