Lagunamycin, a novel 5-lipoxygenase inhibitor. I. Taxonomy, fermentation, physico-chemical properties and biological characteristics.

Abstract

Lagunamycin, a novel 5-lipoxygenase inhibitor, was isolated from the culture broth of Streptomyces sp. AA0310. This compoundshowed potent rat 5-lipoxygenase inhibitory activity (IC50 6.08 um) without lipid peroxidation.As previously described,1~3) a 5-lipoxygenase (5-LPO) inhibitor screen which was composed of a rat 5-lipoxygenase assay and an automated HPLCsystem were successfully employed for analysis of new 5-LPO inhibitory compounds in fermentation broths. In the continued search for 5-LPO inhibitors, Streptomyces sp. AA0310was found to produce a new antibiotic designated lagunamycin. Lagunamycin was produced in good yield by addition of high porous polymer resin in fermentation medium. The active principle was effectively extracted with ethyl acetate from the fermentation broth under acidic conditions and purified by silica gel column chromatography followed by reversed phase silica gel column chromatography. Lagunamycin belonged to a novel family of antibiotics containing a diazo group with potent inhibition against RBL-1 cell's 5-LPO without lipid peroxidation. In this paper, the taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological activities of lagunamycin are reported. Materials and MethodsTaxonomy

Biosynthesis of fatty acid and polyketide metabolites

“…The compounds are believed to arise from the polyunsaturated C,, fatty acid (81), via neolaurencenyne (82), laurencenyne (83), dihydrolaurediols (84), and laurediols (85) and ( 86), all of which exist as 3 2 (a series) and 3 E (b series) mixtures as shown in Scheme 16. Support for the intermediacy of the laurediols (86a) and (86b) was provided by their in vitro conversion to (87) and (88), respectively, in the presence of lactoperoxidase, bromide ions, and hydrogen A more recent paper54 reports the isolation of the putative intermediate diols (84a), (84b), (85a), and (85b) from L. nipponica. These compounds were not enantiomerically pure and their enantiomeric ratios varied.…”

“…The Laurencia algae are rich sources of cyclic halo-ethers such as laureatin (89), deacetyllaurencin (87), prelaureatin (88), and laurallene (90). These cyclic halo-ethers are characterized by a contiguous C,, chain, an eight-membered ether ring system, and a terminal acetylene or allene moiety.…”

Natural products containing a diazo group

“…The compound is a potent inhibitor of 5-lipoxygenase but shows no effect on lipid peroxidation; it also shows modest activity against Gram-positive bacteria. 52 The structure was determined as the unusual diazo-tetraoxoquinoline 18 by a combination of chemical degradation and NMR spectroscopy, although the stereocentre in the side chain was not specified at this point. 53 The structure was confirmed, and the stereochemistry assigned, by total synthesis in 2006 (Scheme 8).…”

Enhanced Isolation of Streptomyces from Different Soil Habitats in Calamba City, Laguna, Philippines using a Modified Integrated Approach

“…In the Philippines, there is a wealth of evidence proving the existence of Streptomyces in soil habitats and the antibiotic-producing ability of the isolated strains. Several antibiotics have been discovered from the different Streptomyces strains isolated from the Philippine soil, such as erythromycin (ilotycin) [ 15 ], roseoflavin [ 16 ], and lagunamycin [ 17 ]. More recent local studies have focused on the isolation of antibiotic-producing Streptomyces from the marine environment [ 18 , 19 ], while others have focused on the agricultural application of the compounds derived from different strains of Streptomyces, such as the promotion of plant growth [ 20 ] and crop protection [ 21 ].…”