[show abstract][hide abstract] ABSTRACT: Natural products produced by microorganisms are important starting compounds for drug discovery. Secondary metabolites, including antibiotics, have been isolated from different Streptomyces species. The production of these metabolites depends on the culture conditions. Therefore, the development of a new culture method can facilitate the discovery of new natural products. Here, we show that mycolic acid-containing bacteria can influence the biosynthesis of cryptic natural products in Streptomyces species. The production of red pigment by Streptomyces lividans TK23 was induced by coculture with Tsukamurella pulmonis TP-B0596, which is a mycolic acid-containing bacterium. Only living cells induced this pigment production, which was not mediated by any substances. T. pulmonis could induce natural-product synthesis in other Streptomyces strains too: it altered natural-product biosynthesis in 88.4% of the Streptomyces strains isolated from soil. The other mycolic acid-containing bacteria, Rhodococcus erythropolis and Corynebacterium glutamicum, altered biosynthesis in 87.5 and 90.2% of the Streptomyces strains, respectively. The coculture broth of T. pulmonis and Streptomyces endus S-522 contained a novel antibiotic, which we named alchivemycin A. We concluded that the mycolic acid localized in the outer cell layer of the inducer bacterium influences secondary metabolism in Streptomyces, and this activity is a result of the direct interaction between the mycolic acid-containing bacteria and Streptomyces. We used these results to develop a new coculture method, called the combined-culture method, which facilitates the screening of natural products.
Applied and environmental microbiology 01/2011; 77(2):400-6. · 3.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alchivemycin A, a novel polycyclic polyketide, was isolated from the culture extract of a plant-derived actinomycete Streptomyces sp. The structure and relative configuration were elucidated by spectroscopic analysis and X-ray crystallography, and the absolute configuration was determined by a (1)H NMR anisotropy method using MPA ester derivatization. The new compound contains an unprecedented heterocyclic ring system, 2H-tetrahydro-4,6-dioxo-1,2-oxazine. Alchivemycin A showed potent antimicrobial activity against Micrococcus luteus and inhibitory effects on tumor cell invasion.
[show abstract][hide abstract] ABSTRACT: Two novel isocoumarins, bacilosarcins A (1) and B (2) were isolated from a culture broth of the marine-derived bacterium Bacillus subtilis TP-B0611. The structures and absolute configurations of 1 and 2 were determined on the basis of spectroscopic analyses and chemical conversions. Compound 1 possesses an unprecedented 3-oxa-6,9-diazabicyclo[3.3.1]nonane ring system while 2 has a 2-hydroxymorpholine moiety that is rare in nature. These compounds showed growth inhibition against barnyard millet.
[show abstract][hide abstract] ABSTRACT: Two novel anthraquinones, lupinacidins A (1) and B (2), have been isolated from the culture broth of a new endophytic actinomycete belonging to the genus Micromonospora. Lupinacidins were found to show significant inhibitory effects on the invasion of murine colon 26-L5 carcinoma cells without inhibiting cell growth.
[show abstract][hide abstract] ABSTRACT: In the screening of antitumor compounds from microbial secondary metabolites, myxochelin A was isolated from a culture broth of Nonomuraea pusilla TP-A0861. The absolute configuration was determined to be S by synthesizing both enantiomers from an L- or D-lysine derivative and comparing their specific rotations. Both enantiomers of myxochelin A showed remarkable inhibitory effects on the invasion of murine colon 26-L5 carcinoma cells at non-cytotoxic concentrations.
The Journal of Antibiotics 12/2006; 59(11):698-703. · 2.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: A new cytotoxic compound, pterocidin, was isolated from the endophytic Streptomyces hygroscopicus TP-A0451, and the structure was determined on the basis of spectroscopic data. Pterocidin showed cytotoxicity against some human cancer cell lines with IC50 values of 2.9-7.1 microM.
The Journal of Antibiotics 04/2006; 59(3):193-5. · 2.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: The biosynthetic gene cluster of goadsporin, a polypeptide antibiotic containing thiazole and oxazole rings, was cloned from Streptomyces sp. TP-A0584. The cluster contains a structural gene, godA, and nine god (goadsporin) genes involved in post-translational modification, immunity and transcriptional regulation. Although the gene organization is similar to typical bacteriocin biosynthetic gene clusters, each goadsporin biosynthetic gene shows low homology to these genes. Goadsporin biosynthesis is initiated by the translation of godA, and the subsequent cyclization, dehydration and acetylation are probably catalysed by godD, godE, godF, godG and godH gene products. godI shows high similarity to the 54 kDa subunit of the signal recognition particle and plays an important role in goadsporin immunity. Furthermore, four goadsporin analogues were produced by site-directed mutagenesis of godA, suggesting that this biosynthesis machinery is used for the heterocyclization of peptides.
[show abstract][hide abstract] ABSTRACT: Indole-3-pyruvic acid was transformed to chromopyrrolic acid by a novel heme-containing enzyme StaD responsible for staurosporine biosynthetic pathway in Streptomyces sp. TP-A0274.
[show abstract][hide abstract] ABSTRACT: The staurosporine biosynthetic gene cluster in Streptomyces sp. TP-A0274 consists of 15 sta genes. In the cluster, it was predicted that staN, which shows high similarity to cytochrome P450 is involved in C-N bond formation between the nitrogen at N-12 of aglycone and the carbon at C-5' of deoxysugar. The staN disruptant produced holyrine A instead of staurosporine. The structure of holyrine A is aglycone linking to 2,3,6-trideoxy-3-aminoaldohexose between N-13 and C-1' of deoxysugar. Holyrine A was converted to staurosporine by the staD disruptant. These results indicate that StaN, cytochrome P450 is responsible for C-N bond formation. This is the first example of C-N bond formation catalyzed by cytochrome P450. In addition, holyrine A was confirmed to be an intermediate of staurosporine biosynthesis, which suggests that the N- and O-methylation at C-3' and C-4' takes place after the formation of the C-N bond between C-5' and N-12 in the biosynthetic pathway.
Bioscience Biotechnology and Biochemistry 10/2005; 69(9):1753-9. · 1.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the screening for muscarinic M3 receptor binding inhibitors from microbial secondary metabolites, the extract of Nocardia nova JCM 6044 was found to be highly active. Bioassay-guided isolation led to the identification of three siderophores, nocardimicins G (1), H (2) and I (3). Their chemical structures were determined by spectroscopic analysis using NMR and MS. 1 and 2 inhibited the binding of tritium-labeled N-methylscopolamine to the muscarinic M3 receptor with Ki values of 0.44 microM and 0.37 microM, respectively, whereas 3 showed no inhibition at 10 microM. 1 and 2 also showed weak binding inhibitory activity to the M5 receptor but not to the M1, M2 and M4 receptors at 10 microM.
The Journal of Antibiotics 10/2005; 58(9):566-72. · 2.19 Impact Factor