Journal
CHEMICAL SCIENCE
Volume 5, Issue 1, Pages 397-402Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3sc52281d
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Funding
- BBSRC [BB/I014039, BB/I014737, BB/E021611, BB/E022367]
- Daiichi Sankyo Co. Ltd [SANK 73390]
- EPSRC [EP/G036764/1]
- AstraZeneca
- GlaxoSmithKline
- Novartis
- Pfizer
- Syngenta
- University of Bristol
- BBSRC [BB/I014039/1, BB/E022367/1] Funding Source: UKRI
- EPSRC [EP/K03927X/1, EP/E000177/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E022367/1, BB/I014039/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/E000177/1, EP/K03927X/1] Funding Source: researchfish
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The biosynthesis of the mixed PKS-FAS-NRPS hybrid antibiotic thiomarinol A was investigated using feeding studies to both wild type and mutant strains of the marine bacterium Pseudoalteromonas. Particularly interesting features of the pathway include assembly of the 8-hydroxyoctanoic acid side-chain via chain extension of a C-4-precursor (4-hydroxybutyrate), and construction of the pyrrothine unit from cysteine via (HolA-D, F-H) prior to intact incorporation into thiomarinol (catalysed by TmlU). A series of thiomarinol-related and other minor metabolites have been isolated from wild-type and mutant strains. The results of these investigations are rationalised in terms of the overall biosynthetic pathway.
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