title: Biosynthetic products from a nearshore-derived gram-negative bacterium enable reassessment of the kailuin depsipeptides.
abstract: Sampling of California nearshore sediments resulted in the isolation of a Gram-negative bacterium, Photobacterium halotolerans, capable of producing unusual biosynthetic products. Liquid culture in artificial seawater-based media provided cyclic depsipeptides including four known compounds, kailuins B-E (2-5), and two new analogues, kailuins G and H (7 and 8). The structures of the new and known compounds were confirmed through extensive spectroscopic and Marfey's analyses. During the course of these studies, a correction was made to the previously reported double-bond geometry of kailuin D (4). Additionally, through the application of a combination of derivatization with Mosher's reagent and extensive (13)C NMR shift analysis, the previously unassigned chiral center at position C-3 of the β-acyloxy group of all compounds was determined. To evaluate bioactivity and structure-activity relationships, the kailuin core (13) and kailuin lactam (14) were prepared by chiral synthesis using an Fmoc solid-phase peptide strategy followed by solution-phase cyclization. All isolated compounds and synthetic cores were assayed for solid tumor cell cytotoxicity and showed only minimal activity, contrary to other published reports. Additional phenotypic screenings were done on 4 and 5, with little evidence of activity.
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Theodore
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lorig-Roach
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Still
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Johnson
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Marija
authors.initials: M
authors.lastname: Drašković
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Schwochert
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Cassandra N
authors.initials: CN
authors.lastname: Naphen
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Crews
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Barker
authors.affiliation: ‡Josephine Ford Cancer Center, Henry Ford Health System, Detroit, Michigan 48202, United States.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Valeriote
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Lokey
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: D001685:Biological Factors / Q000737:chemistry* / Q000302:isolation & purification*; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification*; D006090:Gram-Negative Bacteria / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010776:Photobacterium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001685:Biological Factors; D047630:Depsipeptides