Discovery of gargantulides B and C, new 52-membered macrolactones from Amycolatopsis sp. Complete absolute stereochemistry of the gargantulide family. Issue 2 (15th December 2021)

• Record Type: Journal Article
• Authors: Carretero-Molina, Daniel; Ortiz-López, Francisco Javier; Gren, Tetiana; Oves-Costales, Daniel; Martín, Jesús; Román-Hurtado, Fernando; Sparholt Jørgensen, Tue; de la Cruz, Mercedes; Díaz, Caridad; Vicente, Francisca; Blin, Kai; Reyes, Fernando; Weber, Tilmann; Genilloud, Olga
• Is Part Of: Organic chemistry frontiers. Volume 9:Issue 2(2022)
• Page Start: 462
• Page End: 470
• Publication Date: 2021-12-15
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1039/d1qo01480c
• Languages: English
• ISSNs: 2052-4110

Abstract

Abstract : Gargantulides B and C are among the most complex bacterial polyketides discovered so far. A combination of NMR and genome-based bioinformatics analyses allowed us to complete and revise the absolute stereochemistry of the entire gargantulide family. Abstract : 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 β-glucopyranose and/or α-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 .