16-Methyloxazolomycin, a New Antimicrobial and Cytotoxic Substance Produced by a Streptomyces sp.

Abstract

Triene antibiotics containing /Mactone-y-lactam bicyclospiro and oxazole rings are unique metabolites produced by Streptomyces spp., such as oxazolomycins1'2) and curromycins.3'4)In the course of our continuing search for novel antimicrobial agents from microorganisms, an actinomycete strain Streptomyces sp. isolated from a soil sample collected in Taejon, Korea, was found to produce a new antibacterial 16-methyloxazolomycin (1). In this paper, we describe the production, isolation, structural elucidation and biological activities of 1. The strain was cultured in the seed mediumconsisting of glucose 2%, starch 1%, soybean flour 2.5%, yeast extract 0.4%, NaCl 0.2%, K2HPO4 0.005% and beef extract 0.1% (adjusted to pH 7.3 before sterilization).The seed culture was carried out on a rotary shaker (250rpm) at 28°C for 24 hours in 500-ml Erlenmeyer flasks containing 100ml of the seed medium. Then, the seed culture (100ml) was inoculated to a 50-liter jar fermenter containing 10 liters of the production medium (antifoam 0.08%). Fermentation was carried out at 27°C for 4 days with aeration (10 liters/minute) under constant agitation (250 rpm).The isolation of 16-methyloxazolomycin was guided by the use of Bacillus subtilis IAM1069 as a test organism. The culture broth was centrifuged to separate the mycelial cake. The mycelial cake was stirred overnight in 70% aqueous acetone (5 liters) and filtered. The filtrate was concentrated in vacuo to remove the organic solvent, DEC. 1997 resulting in an aqueous solution.

Structural Studies and Antifungal Activity of Unique Polyene Amides, Clathrynamide A and Three New Derivatives, from a Marine Sponge,PsammoclemmaSp.

“…1) The distinctive structure consists of a highly unsaturated C-20 carbon chain with a dienyne moiety and methyl branches of biosynthetic interest. Only two examples of this type with a C-20 carbon skeleton are known other than 1, 1) although a series of related compounds that possess the right-half (C1-C9 moiety) of 1 have been discovered from actinomycetes, e.g., phthoxazolins (or inthomycins), [2][3][4][5] oxazolomycins, [6][7][8][9][10][11] and curromycins. 12,13) In our search for novel antifungal metabolites from marine organisms, 1 was rediscovered from an Okinawan marine sponge of Psammoclemma sp.…”

The oxazolomycin family: a review of current knowledge

“…3 Curromycin A and curromycin B were formerly termed as triedimycin A and triedimycin B. 4 In 1997 16-methyloxazolomycin (5) was isolated as a product from Streptomyces sp. as another member of the oxazolomycin family.…”

“…as another member of the oxazolomycin family. 5 Two novel oxazolomycins, specically oxazolomycin B (3) and oxazolomycin C (4) were reported in 1998 by Kanzaki et al as the products of Streptomyces albus JA3453. 6 Otani et al in 2000 reported isolation of KSM-2690 B (8) and KSM-2690 C (9) from the broth ltrate of Streptomyces strain KSM-2690 and they were classied as novel oxazolomycins.…”

“…Additionally, compound 6 contains -CH 2 OMe residue at C16-position and compound 7 possesses the methyl group at the same position C16. 3 Kim et al reported in 1997 isolation, structural elucidation and biological properties of 16-methyloxazolomycin (5), with partial stereochemical determination. 5 Structural recognition of 5 revealed considerable similarities with the structure of 1.…”

A new 16-membered tetraene macrolide JBIR-100 from a newly identified Streptomyces species

“…A search in AntiBase [61] using the above spectral data of compound 262 resulted in lajollamycin [394] as the sole known structure (Table 36). The identity with lajolamycin (262) [395] 16-methyloxazolomycin [396] (265), and triedimycin B6 (266) were previously isolated from bacteria. Lajollamycin (262) was isolated from the marine actinomycete Streptomyces nodosus (NPS007994); it is a potent antimicrobial agent against both against drug-sensitive and -resistant Gram-positive bacteria, as well as an in vitro inhibitor of B16-F10 tumor cells [394] .…”