title: Discovery of the lomaiviticin biosynthetic gene cluster inSalinispora pacifica.
abstract: 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 inSalinispora pacificastrains DPJ-0016 and DPJ-0019 using a combination of molecular approaches and genome sequencing. The link between thelomgene 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.
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Janso
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Haltli
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Eustáquio
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Kerry
authors.initials: K
authors.lastname: Kulowski
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, United States.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Waldman
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Zha
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, United States.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Bernan
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Haiyin
authors.initials: H
authors.lastname: He
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Guy T
authors.initials: GT
authors.lastname: Carter
authors.affiliation: Natural Products, Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Groton, CT 06355, United States.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Koehn
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, United States.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Balskus
keywords: Comparative genomics; Diazo group; Dimerization; Natural product biosynthesis; Polyketide