Okilactomycin, a novel antibiotic produced by a Streptomyces species. I. Taxonomy, fermentation, isolation and characterization.

Abstract

Okilactomycin, a novel antibiotic, was isolated from the culture filtrate of a strain of actinomycetes. The producing organism, strain YP-02908L, was identified as Streptomyces griseoflavus subsp. zamamiensis subsp. nov. The antibiotic was extracted with ethyl acetate and purified by silica gel column chromatography. It was obtained as colorless prisms from a dichloromethane solution. It exhibited weak antimicrobial activity against Grampositive organisms in vitro. It also exhibited antitumor activity against Ehrlich ascites carcinoma in vivo. The apparent molecular formula of okilactomycin was determined as C24H32O6.It is a new memberof the lactone group antibiotics. 1475 In the course of our screening for new antibiotics, a novel antibiotic, okilactomycin, was found. The antibiotic was produced by Streptomyces griseoflavus subsp. zamamiensis subsp. nov. It exhibited weak antimicrobial activity against Gram-positive organisms and antitumor activity agaist Ehrlich ascites carcinoma. In this paper, we describe the taxonomy of the producing organism, the fermentation, isolation and characterization of the antibiotic. Materials and Methods Chemicals Chemicals employed were as follows: Kieselgel 60 and TLC plates Silica gel 60 F254 (0.25 mm thickness) from E. Merck, Darmstadt, FRG; Sephadex LH-20 from Pharmacia Fine Chemicals, Sweden; mitomycin C from KyowaHakko Kogyo Co., Ltd., Japan. All other chemicals were of analytical grade. Components for Media Components for media employed were as follows :

Discovery of okilactomycin and congeners from Streptomyces scabrisporus by antisense differential sensitivity assay targeting ribosomal protein S4

“…The 13 C NMR spectrum ( 21.2) indicated differences between the two compounds. The proton and carbon chemical shifts of C-17 shifted significantly upfield due to the absence of conjugation.…”

“…MIC data observed in this study are consistent with that reported earlier. 21 Compound 1 did not show activity against Gram-negative bacteria, but did inhibit growth of the Escherichia coli (envA/tolC) strain, which harbors mutated membrane and efflux pump, and showed an MIC of 64 mg ml À1 . The other four compounds were significantly less active in this assay with only 5 showing a weak activity against S. pneumoniae and also E. coli.…”

Chapter 11. Novel Approaches to Exploit Natural Products from Microbial Resources

“…The compound was also described as cytotoxic against some leukemia cell lines with IC 50 ranging from 0.09 to 0.037 mg/mL. 69 Okilactomycin and four congeners okilactomycin A, B, C and D (21)(22)(23)(24) were recently described by our group as produced by a strain of Streptomyces scabrisporus. 70 These compounds were identified from the twoplate antisense RpsD screening where okilactomycin remained the most active compound inhibiting Streptococcus pneumoniae (MIC of 8-16 mg/mL), Enterococcus faecalis (MIC of 16 mg/mL) and Bacillus subtilis (MIC of 4-16 mg/mL).…”

In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationships

“…14 Okilactomycin is a polyketide compound reported to have antitumor and weak antibacterial activity. 15 Recently, Zhang et al 16 confirmed that its mode of action in bacterial cells is via inhibition of RNA synthesis. Piloquinone is a phenanthrenequinone and exhibits antibacterial activity, 17 although the mode of action is not known.…”