Micromonosporamide A with Glutamine-Dependent Cytotoxicity from Micromonospora sp. MM609M-173N6: Isolation, Stereochemical Determination, and Synthesis

Abstract

An acyldipeptide, micromonosporamide A, was isolated from the fermentation broth of Micromonospora sp. MM609M-173N6 by bioassay-guided fractionation using a glutamine compensation assay. The planar structure was elucidated on the basis of comprehensive one-and two-dimensional nuclear magnetic resonance and high-resolution mass spectrometry. The relative and absolute configuration of the entire molecule were determined using a combined approach, involving chromatographic analysis by liquid chromatography−mass spectrometry, advanced Marfey's method, and total synthesis. Micromonosporamide A exhibited glutamine-dependent antiproliferative activity.

Marine natural products

“…and was shown to display glutamine-dependent cytotoxicity. 15 Another Micromonospora study afforded a new enteromycin-class antibiotic, akazaoxime 44 , that possessed an aldoxime functionality. The related congener, A-76356 45 , isolated from a marine source for the first time, was also reported.…”

Micromonospora: A Prolific Source of Bioactive Secondary Metabolites with Therapeutic Potential

“…nigra NRRL 3097 in 1967. 177 Rifamycins S (191) and SV (192) were both isolated from strains M. chalcea ATCC 21994 and M. lacustris ATCC 21974, and the latter strain was also found to produce the 3-thiomethyl derivatives 193 and 194. 178,179 Another rifamycin derivative (197) that showed a similar antibacterial spectrum to 191 against several pathogenic bacteria was generated by the mutant TP-A0468 through the deletion of the kosinostatin (KST) BGC.…”

“…69 afforded two cyclic dipeptides with potent antibacterial activity against MRSA ( 207 and 208 ) . K-13 ( 209 ), which consists of a tyrosine and an unusual diamino dicarboxylic acid, was identified as a novel promising inhibitor of angiotensin I converting enzyme (ACE), , while micromonosporamide A ( 210 ), produced by the strain MM609M-173N6, exhibited glutamine-dependent antiproliferative activity …”

Phenopyrrolizins A and B, Two Novel Pyrrolizine Alkaloids from Marine-Derived Actinomycetes Micromonospora sp. HU138

“…Micromonospora, one of the most important actinomycetes genera, is a valuable repository of natural bioactive ingredients [1]. Micromonospora-derived secondary metabolites include a large and structurally diverse class of metabolites such as macrolides [2,3], peptides [4,5], aminoglycosides [6,7], macrolactams [8][9][10], alkaloids [11,12], quinones [13][14][15], oligosaccharides [16,17], and miscellaneous compounds [18,19], some of which have developed as important products of the pharmaceutical industry, for example, gentamicin, erythromycin B, and sisomicin [1,20,21]. However, the rate of discovery of new secondary metabolites from Micromonospora has been rapidly decreasing in the past two decades, and the discovery of new pharmaceutical compounds from Micromonospora has become more difficult [1].…”