Journal:

Article Title: Antibacterial agents that inhibit two-component signal transduction systems

doi:

Figure Lengend Snippet: Minimal inhibitory concentrations of RWJ-49815 and analogs against Gram-positive bacteria

Article Snippet: However, polymyxin B nonapeptide-treated E. coli ( 33 ) were highly sensitive to RWJ-49815 (MICs of 1–2 μg/ml, data not shown), suggesting that the outer membrane of Gram-negative bacteria is a barrier to penetration of the compound into the cells. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 caption a7 Structures of RWJ-49815 and analogs. table ft1 table-wrap mode="anchored" t5 Table 1 caption a7 Minimal inhibitory concentrations, * μg/ml Test organism RWJ-49815 † RWJ-49619 RWJ-49640 RWJ-60953 S. aureus ATTC 29213 1 4 4 16 S. aureus ATTC 6538 2 2 1 >32 S. aureus OC667 (MR) 2 2 2 >32 S. aureus OC2089 (MR) 2 2 1 >32 S. epidermidis OC2603 2 2 2 >32 E. faecalis ATCC 29212 2 4 8 >32 E. faecalis OC3041 2 4 8 >32 E. faecium OC3312 (VanR) 1 4 8 >32 S. pneumoniae OC3570 (PenS) 2 16 8 >32 S. pneumoniae OC3561 (PenI) 2 8 4 >32 S. pneumoniae OC3035 (PenR) 1 8 4 >32 Open in a separate window * Stock solutions of the compounds were prepared in dimethyl sulfoxide at 2.56 mg/ml and MICs were determined with the broth micro-dilution method as described by the National Committee for Clinical Laboratory Standards (1994) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically.

Techniques:

Journal: ACS chemical biology

Article Title: Discovery of the Tyrobetaine Natural Products and Their Biosynthetic Gene Cluster via Metabologenomics

doi: 10.1021/acschembio.7b01089

Figure Lengend Snippet: Structure elucidation of tyrobetaine and chlorotyrobetaine. (a) The structure of tyrobetaine and chlorotyrobetaine with key NMR correlations indicated. (b) The MS2 spectrum for tyrobetaine with key masses indicated. *Indicates the mass after removal of the trimethylammonium. LOH = hydroxyleucine. Red masses indicate observed masses. Δppm values are indicated in parentheses after the key masses. Key mass losses are in purple.

Article Snippet: We expect that tyrobetaine does have a biological function that we have yet to discover. table ft1 table-wrap mode="anchored" t5 caption a7 organism/protease tyrobetaine MIC b or IC 50 c ( μ M) chlorotyrobetaine MIC b or IC 50 c ( μ M) oxytetracycline MIC ( μ g/mL) oxytetracycline + 32 μ g/mL tyrobetaine MIC ( μ g/mL) E. faecalis ATTC 19433 >100 >100 ND ND S. aureus ATCC 29213 >100 >100 ND ND K. pneumoniae ATCC 27736 >100 >100 ND ND A. baumannii ATCC 19606 >100 >100 ND ND P. aeruginosa PAO1 >100 >100 ND ND E. coli ATCC 25922 >100 >100 4 8 A549 human lung cancer >100 >100 ND ND ACE >10 ND ND ND HIV-1 protease >10 ND ND ND Open in a separate window a ND = not determined.

Techniques:

Journal: ACS chemical biology

Article Title: Discovery of the Tyrobetaine Natural Products and Their Biosynthetic Gene Cluster via Metabologenomics

doi: 10.1021/acschembio.7b01089

Figure Lengend Snippet: Tyrobetaine BGC and heterologous expression. (a) The BGC for the tyrobetaines from Streptomyces sp. WC-3703. Arrows indicate genes. The color of the arrow corresponds to the type of gene (indicated below the arrows). See Table S5 for BLAST analysis. (b) AntiSMASH NRPS domain predictions for TybD, TybE, and TybF. A = adenylation domain with subscript indicating the predicted amino acid (Y = tyrosine, X = no consensus, A = alanine). MT = N-methyltransferase. T = thiolation domain. C = condensation domain. See Table S6 for NRPS adenylation domain predictions. (c) Extracted ion chromatogram for tyrobetaine (587.30–587.31) in wild type S. lividans 66, S. lividans 66 pRAM6 (heterologous expression of NRPS_GCF.432), purified tyrobetaine, and S. lividans 66 pRAM6 spiked with purified tyrobetaine.

Article Snippet: We expect that tyrobetaine does have a biological function that we have yet to discover. table ft1 table-wrap mode="anchored" t5 caption a7 organism/protease tyrobetaine MIC b or IC 50 c ( μ M) chlorotyrobetaine MIC b or IC 50 c ( μ M) oxytetracycline MIC ( μ g/mL) oxytetracycline + 32 μ g/mL tyrobetaine MIC ( μ g/mL) E. faecalis ATTC 19433 >100 >100 ND ND S. aureus ATCC 29213 >100 >100 ND ND K. pneumoniae ATCC 27736 >100 >100 ND ND A. baumannii ATCC 19606 >100 >100 ND ND P. aeruginosa PAO1 >100 >100 ND ND E. coli ATCC 25922 >100 >100 4 8 A549 human lung cancer >100 >100 ND ND ACE >10 ND ND ND HIV-1 protease >10 ND ND ND Open in a separate window a ND = not determined.

Techniques: Expressing, Purification

Journal: ACS chemical biology

Article Title: Discovery of the Tyrobetaine Natural Products and Their Biosynthetic Gene Cluster via Metabologenomics

doi: 10.1021/acschembio.7b01089

Figure Lengend Snippet: Feeding experiments with stable isotope labeled amino acids. Mass spectrum from spent media from Streptomyces sp. NRRL WC-3703 grown on (a) medium alone or medium with (b) D4-L-tyrosine, (c) D3,13C-methionine, (d) D10-L-leucine, or (e) D4-L-alanine. (f) Structure of tyrobetaine with likely location of stable isotopes. Yellow bar indicates the m/z for tyrobetaine. Colored bars indicate isotopically labeled tyrobetaine. See Figure S6 for chlorotyrobetaine.

Article Snippet: We expect that tyrobetaine does have a biological function that we have yet to discover. table ft1 table-wrap mode="anchored" t5 caption a7 organism/protease tyrobetaine MIC b or IC 50 c ( μ M) chlorotyrobetaine MIC b or IC 50 c ( μ M) oxytetracycline MIC ( μ g/mL) oxytetracycline + 32 μ g/mL tyrobetaine MIC ( μ g/mL) E. faecalis ATTC 19433 >100 >100 ND ND S. aureus ATCC 29213 >100 >100 ND ND K. pneumoniae ATCC 27736 >100 >100 ND ND A. baumannii ATCC 19606 >100 >100 ND ND P. aeruginosa PAO1 >100 >100 ND ND E. coli ATCC 25922 >100 >100 4 8 A549 human lung cancer >100 >100 ND ND ACE >10 ND ND ND HIV-1 protease >10 ND ND ND Open in a separate window a ND = not determined.

Techniques: Labeling

Journal: ACS chemical biology

Article Title: Discovery of the Tyrobetaine Natural Products and Their Biosynthetic Gene Cluster via Metabologenomics

doi: 10.1021/acschembio.7b01089

Figure Lengend Snippet: Antibiotic Activity, Anticancer Activity, and Protease Inhibition of Tyrobetaine and Chlorotyrobetaine a

Article Snippet: We expect that tyrobetaine does have a biological function that we have yet to discover. table ft1 table-wrap mode="anchored" t5 caption a7 organism/protease tyrobetaine MIC b or IC 50 c ( μ M) chlorotyrobetaine MIC b or IC 50 c ( μ M) oxytetracycline MIC ( μ g/mL) oxytetracycline + 32 μ g/mL tyrobetaine MIC ( μ g/mL) E. faecalis ATTC 19433 >100 >100 ND ND S. aureus ATCC 29213 >100 >100 ND ND K. pneumoniae ATCC 27736 >100 >100 ND ND A. baumannii ATCC 19606 >100 >100 ND ND P. aeruginosa PAO1 >100 >100 ND ND E. coli ATCC 25922 >100 >100 4 8 A549 human lung cancer >100 >100 ND ND ACE >10 ND ND ND HIV-1 protease >10 ND ND ND Open in a separate window a ND = not determined.

Techniques: Activity Assay, Inhibition