Revision of the Structure Assigned to the Antibiotic BU-4664L from Micromonopora

Abstract

The structure assigned to the antitumor antibiotic BU-4664L from Micromonospora sp. was revised to 5,10-dihydro-4,6,8-trihydroxy-10-(3,7,11-trimethyltrans-2,trans-6,10-dodecatrienyl)-11H-dibenzo[b,e][1,4]-diazepin-11-one based on the NMR analysis. Keywords BU-4664L, antitumor, MicromonosporaIn the screening of antitumor compounds from rare actinomycetes, Micromonospora sp. TP-A0860 was found to produce BU-4664L [1] and rakicidins [2]. BU-4664L was originally isolated from Micromonospora sp. M990-6 as a lipoxygenase inhibitor and was shown to have potent in vitro and in vivo antitumor activity. The structure of BU-4664L is described in a patent as shown ( Fig. 1). During the structural confirmation of the compounds produced by strain TP-A0860, we found that the proposed structure of BU-4664L was incorrect. We herein report the revision of the structure of BU-4664L on the basis of NMR analysis.The producing strain was isolated from a soil sample collected in Osawano, Toyama, Japan and identified as Micromonospora sp. based on the taxonomic study. Seed and production fermentation was carried out in V-22 and A-3M medium, respectively, as described previously [3]. The fermentation broth (5 liters) was extracted with 1-butanol and the organic layer was concentrated in vacuo. The oily extract (17 g)

Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete

“…046Eco-11 (Figure S2E). 39 The dibenzodiazepinone core of diazepinomicin is very rare among natural products and to date has only been reported to be produced by Micromonospora strains 15 ,. 16 , 39 Recently discovered BGCs in Streptomyces griseoflavus Tü4000 and in Streptomyces sp.…”

Characterization and screening of antimicrobial activity of Micromonospora strains from Thai soils

“…The fermentation broth was extracted for preliminary characterization of secondary metabolites. We found that only isolate AL7-5 which was identified as M. chalcea could produce rakicidin (McBrien et al, 1995) (Figure 3a) when cultivated on A3M, A11M and A16 and produced compound BU4664L (Figure 3b) only on A16 (Igarashi et al, 2005). 1(2)…”

Unusual N-Prenylation in Diazepinomicin Biosynthesis: The Farnesylation of a Benzodiazepine Substrate Is Catalyzed by a New Member of the ABBA Prenyltransferase Superfamily

“…Diazepinomicin has been independently isolated from different Micromonospora strains from different geographic locations of this world by Bristol-Myers Squibb [10,11], Thallion Pharmaceuticals (formerly Ecopia BioSciences) [12], Wyeth [13] and recently by Abdelmohsen et al [14]. So far this compound has never been described outside of the genus Micromonospora .…”