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

Authors

Christine M. Theodore, University of California, Santa Cruz, California, USAFollow
Nicholas Lorig-Roach, University of California, Santa Cruz, California, USAFollow
Patrick C. Still, University of California, Santa Cruz, California, USAFollow
Tyler A. Johnson, University of California, Santa Cruz, California, USAFollow
Marija Drašković, University of California, Santa Cruz, California, USAFollow
Joshua A. Schwochert, University of California, Santa Cruz
Cassandra N. Naphen, University of California, Santa CruzFollow
Mitchell S. Crews, University of California, Santa CruzFollow
Simone A. Barker, University of California, Santa Cruz
Frederick A. Valeriote, Henry Ford Hospital, Detroit, Michigan
R. Scott Lokey, University of California, Santa Cruz
Phillip Crews, University of California, Santa CruzFollow

Department

Natural Sciences and Mathematics

Document Type

Article

Source

Journal of Natural Products

Publication Date

3-27-2015

ISSN

1520-6025

Volume

78

Issue

3

First Page

441

Last Page

452

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.

PubMed ID

25699470

Rights

Copyright © 2015 The American Chemical Society and American Society of Pharmacognosy

Publisher's Statement

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Natural Products, copyright © American Chemical Society after peer review and technical editing by the publisher.