Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355

Bernhard Kepplinger, Lina Mardiana, Joseph Cowell, Stephanie Morton-Laing, Yousef Dashti, Corinne Wills, Emma C.L. Marrs, John D. Perry, Joe Gray, Michael Goodfellow, Jeff Errington, Michael R. Probert, William Clegg, Jonathan Bogaerts, Wouter Herrebout, Nick E.E. Allenby, Michael J. Hall

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152. Structural elucidation, including absolute stereochemical assignment, was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Cytological profiling experiments suggest a putative antibiotic mode-of-action, involving membrane depolarisation and chromosomal decondensation of the target bacteria.

Original languageEnglish
Article number15579
JournalScientific reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

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