Isolation and structure elucidation of lipopeptide antibiotic taromycin B from the activated taromycin biosynthetic gene cluster.
Kirk A ReynoldsHanna LuhavayaJie LiSamira DaheshVictor NizetKazuya YamanakaBradley S MoorePublished in: The Journal of antibiotics (2017)
In the ongoing effort to unlock the chemical potential of marine bacteria, genetic engineering of biosynthetic gene clusters (BGCs) is increasingly used to awake or improve expression of biosynthetic genes that may lead to discovery of novel bioactive natural products. Previously, we reported the successful capture, engineering and heterologous expression of an orphan BGC from the marine actinomycete Saccharomonospora sp. CNQ-490, which resulted in the isolation of the novel lipopeptide antibiotic taromycin A. Herein we report the isolation and structure elucidation of taromycin B, the second most abundant product of the taromycin biosynthetic series, and show that taromycins A and B exhibit complex chromatographic properties indicative of interconverting conformations. Taromycins A and B display potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium clinical isolates, suggestive that the taromycin molecular scaffold is a promising starting point for further derivatization to produce compounds with promising antibiotic characteristics.
Keyphrases
- methicillin resistant staphylococcus aureus
- genome wide
- poor prognosis
- copy number
- genome wide identification
- staphylococcus aureus
- simultaneous determination
- dna methylation
- small molecule
- ms ms
- binding protein
- biofilm formation
- high throughput
- deep brain stimulation
- gas chromatography mass spectrometry
- high performance liquid chromatography
- mass spectrometry
- pseudomonas aeruginosa
- liquid chromatography
- tandem mass spectrometry
- single cell
- bioinformatics analysis