Journal
TETRAHEDRON
Volume 70, Issue 27-28, Pages 4156-4164Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tet.2014.03.009
Keywords
Natural product biosynthesis; Comparative genomics; Diazo group; Polyketide; Dimerization
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Funding
- National Institutes of Health (NIH) [_100000002, DP2 GM105434, GM095450]
- Searle Scholars Program
- Herchel Smith Fellowship
- Harvard University
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The lomaiviticins are a family of cytotoxic marine natural products that have captured the attention of both synthetic and biological chemists due to their intricate molecular scaffolds and potent biological activities. Here we describe the identification of the gene cluster responsible for lomaiviticin biosynthesis in Salinispora pacifica strains DPJ-0016 and DPJ-0019 using a combination of molecular approaches and genome sequencing. The link between the lom gene cluster and lomaiviticin production was confirmed using bacterial genetics, and subsequent analysis and annotation of this cluster revealed the biosynthetic basis for the core polyketide scaffold. Additionally, we have used comparative genomics to identify candidate enzymes for several unusual tailoring events, including diazo formation and oxidative dimerization. These findings will allow further elucidation of the biosynthetic logic of lomaiviticin assembly and provide useful molecular tools for application in biocatalysis and synthetic biology. (C) 2014 Elsevier Ltd. All rights reserved.
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