Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibiotics

• DOI: 10.1099/mic.0.070995-0
• Publication Date: 2013-09-17T02:21:07Z
• Authors: Tadeja Lukežič; Urška Lešnik; Ajda Podgoršek; Jaka Horvat; Tomaž Polak; Martin Šala; Branko Jenko; Peter Raspor; Paul R. Herron; Iain S. Hunter; Hrvoje Petković
• Keywords: Gene cluster; Polyketide synthase; Aromatization

Tetracyclines (TCs) are medically important antibiotics from the polyketide family of natural products. Chelocardin (CHD), produced by Amycolatopsis sulphurea, is a broad-spectrum tetracyclic antibiotic with potent bacteriolytic activity against number Gram-positive and Gram-negative multi-resistant pathogens. CHD has an unknown mode action that different TCs. It some structural features define it as 'atypical' and, notably, active tetracycline-resistant Identification characterization chelocardin biosynthetic gene cluster A. sulphurea revealed 18 putative open reading frames including type II synthase. Compared to typical TCs, chd contains relate its classification 'atypical': additional for two-component cyclase/aromatase may be responsible aromatization pattern, aminotransferase C-4 opposite stereochemistry TCs C-9 methylase unique feature this within Collectively, these enzymes deliver molecule ring C results in unusual planar structure TC backbone. This likely contributor action. In addition biosynthesis primed acetate, unlike which malonamate, offers engineering platform represents opportunity efficient generation novel backbones using combinatorial biosynthesis.