Biosynthetic products from a nearshore-derived gram-negative bacterium enable reassessment of the kailuin depsipeptides

Document Type

Article

Publication Date

3-27-2015

Publication Title

Journal of natural products

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.

Medical Subject Headings

Biological Factors; Depsipeptides; Gram-Negative Bacteria; Humans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Photobacterium; Structure-Activity Relationship

PubMed ID

25699470

Volume

78

Issue

3

First Page

441

Last Page

452

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