Six antitumor antibiotics of a new structure class, indoxamycins A-F (1-6), were isolated from a saline culture group of marine-derived actinomyces whose strains showed approximately 96% sequence homology of 16S rDNA with the family streptomycetaceae. The structures of these indoxamycins, which are unusual polyketides composed of six consecutive chiral centers, were assigned by combined spectral and chemical methods. In feeding experiments using a stable isotope label, indoxamycin A was assembled from propionate units initially forming the "aglycon" pentamethyl indeno furan. The discovery of these unprecedented compounds from marine-derived actinomycetes, a low gene homology genus, offers a significant opportunity for drug discovery.
Nine new 26-membered macrolides of the oligomycin subfamily, neomaclafungins A-I, were isolated from the fermentation broth of Actinoalloteichus sp. NPS702, which was isolated from marine sediment collected from Usa Bay, Kochi Prefecture, Japan. Their structures were identified through mass spectrometry and NMR experiments. They belong to the oligomycin class and have several distinct features including the presence of alkane or alkanol branches. Neomaclafungins A-I exhibited significant antifungal activity in vitro against Trichophyton mentagrophytes (ATCC 9533), showing MIC values between 1 and 3 μg/mL.
A marine-derived actinomyces strain (NPS554) isolated from a marine sediment sample collected from Miyazaki Harbor, Japan, at a depth of 38 m yielded two trialkyl-substituted aromatic acids, lorneic acid A (1) and lorneic acid B (2). The structures of the lorneic acids, which were elucidated by spectroscopic analysis, differed only in the side-chain, which contained either a conjugated double bond or a benzylic alcohol. Their structural differences affected inhibition activities against phosphodiesterase 5.
Microorganisms are capable of producing a broad spectrum of secondary metabolites, and over the past five decades, the prokaryotic actinomycetes have been the most fruitful source of antibiotics, yielding 65-70% of all discovered antibiotics. 1 Therefore, screening of microorganisms for the production of new antibiotics continues to be an important approach in modern drug discovery programs. On the other hand, it is known that actinomycetes produce secondary metabolites of uncertain function, which led us to infer that the componential analysis of culture solution can be the most efficient way to search for the undiscovered compounds of uncertain function. During our research on analyzing secondary metabolites from marine microorganisms, 2 we explored the metabolites from the culture solution of actinomycete strain NPS887 with characteristic peaks on LC-TOF-MS and spots on TLC (0.2 mm, Silica gel 60 F 254 ; Merck, Darmstadt, Germany) over time. Isolation and structure elucidation of the TLC positive metabolites resulted in the identification of two novel aliphatic d-lactone compounds (1, 2, Figure 1a). Surprisingly, the planar structure of 1 was the same as that of invictolide, queen recognition pheromone of the red imported fire ant. Invictolide, exhibiting pheromone activity in both levorotatory and the racemic forms, was isolated from the red imported fire ant queens, Solenopsis invicta (Buren). Its relative stereochemistry was proposed by Rocca et al., 3 and its absolute stereochemistry was established to have (3R,5R,6S,7R)-configuration by Mori's group. 4 Having a great interest on the stereochemistry and biosynthetic pathway of d-lactone compounds (1, 2), microbially derived invictolide diastereomer and its analog, we focus our attention on the analysis of stereochemistry and biosynthetic origin. This report describes the isolation, structural elucidation and biosynthetic origin of tri-epi-invictolide and its analog.The producing strain NPS887 was isolated from marine sediments at a depth of 28 m in the Uranouchi Bay, Kochi, Japan. The 16S rDNA sequence of the NPS887 strain (1409 base pairs) was deposited in the DDBJ Genbank (DDBJ accession number AB601427). This strain shared 98% 16S rDNA sequence identity with Nocardiopsis tangguensis strain HBUM 174826. Strain NPS887 was cultured in 500 ml baffled shake flasks containing 100 ml of the production modified KG medium containing 0.8% glucose (Wako Pure Chemical Industries, Osaka, Japan), 0.8% maltose monohydrate (Wako Pure Chemical Industries), 0.8% soluble starch (Wako Pure Chemical Industries), 1.5% soytone (Becton, Dickinson and Company, Sparks, MD, USA), 0.2% yeast extract (Becton, Dickinson and Company) and 1.8% artificial seawater (Nihon Pharmaceutical, Tokyo, Japan) while shaking at 220 r.p.m., 28.5 1C for 8 days. At the end of the fermentation period, the whole culture broth (1800 ml) was extracted with equal amount of EtOAc. The EtOAc extract, which showed many spots on TLC by anisaldehyde reagent, was subjected to two chromatographic purification ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.