8 research outputs found
Biosynthesis and Structure–Activity Relationship Studies of Okaramines That Target Insect Glutamate-Gated Chloride Channels
Prenylated
indole alkaloid okaramines selectively target insect
glutamate-gated chloride channels (GluCls). Because of their highly
complex structures, including azocine and azetidine rings, total synthesis
of okaramine A or B has not been achieved, preventing evaluation of
the biological activities of okaramines. Biosynthetic approaches provide
alternatives to accessing structurally diverse derivatives and enabling
the elucidation of structure–activity relationships. To explore
the biosynthetic potential of okaramines, gene knockout experiments
of an okaramine-producer fungus were performed. The deletion mutants
of the oxygenase genes <i>okaB</i>, <i>okaD</i>, <i>okaE</i>, and <i>okaG</i> provided analogues
that were unlikely to be accumulated in the normal biosynthetic process
of the wild-type strain. Analysis of the structure–activity
relationships of okaramines collected from the fungal cultures revealed
that 1,4-dihydroazocine and <i>N</i>-aliphatic group attached
to the indole were crucial for GluCl-activating activity. This provided
insights into further derivatization of the complex structure of okaramines
in order to facilitate the development of new insecticides
Phylogenetic tree of complete and partial G genes from 235 Philippine rabies virus strains.
<p>The phylogenetic tree of 233 complete (1572 nt) and two partial (1549 nt) G genes was constructed using the maximum-likelihood method and bootstrap values were calculated from 500 replicates. The three major clades, Luzon (green), Visayas (blue), Mindanao (orange), and two distinct genogroups, Mindoro (pink), and South Luzon (yellow), are indicated with different colors. Dots on the map indicate the number and collection sites of each sample (one dot = one sample). Bootstrap values of greater than 90% are presented.</p
Comparison between phylogenetic trees of rabies virus N and G genes.
<p>Comparison of rabies virus phylogenetic trees for the (A) partial N gene (1124 nt) and the (B) complete G gene (1572 nt) using 57 virus strains from the Philippines and other Asian countries. The trees were constructed using the maximum-likelihood method and bootstrap values were calculated from 500 replicates. Both trees show the three major clades, Luzon (green line), Visayas (blue line), and Mindanao (orange line), and the two distinct strains from Mindoro and South Luzon. The red circle shows the Philippine strain (RV/04030PHI/2004) <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002144#pntd.0002144-Bourhy1" target="_blank">[16]</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002144#pntd.0002144-Ming1" target="_blank">[19]</a> from the cluster that was previously named Asian 2b by Gong et al <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002144#pntd.0002144-Ming1" target="_blank">[19]</a>.</p
Geographic distribution of clade L.
<p>The phylogenetic tree for the G gene from 235 Philippine strains was constructed using the maximum-likelihood method and bootstrap values were calculated from 500 replicates. The condensed tree with the cut off value of 80% is presented and clade L is enlarged. There were nine subclades and three genogroups in clade L.</p
Geographic distribution of subclade L8.
<p>Subclade L8 in the phylogenetic tree of G genes from 235 Philippine strains is enlarged. L8 was further divided into two subclades, L8a and L8b. The topographical imagery in Luzon Island is shown with a green line. A condensed tree with a cut off value of 80% is presented.</p
List of rabies virus samples obtained from other countries.
<p>The reference strains that were used from the Genbank to create <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002144#pntd-0002144-g002" target="_blank">Figure 2</a> have been listed. The cluster was determined by Gong et al (2009).</p
Geographic distribution of clade V and M.
<p>Clades V and M in the phylogenetic tree of the G gene from 235 Philippine strains is enlarged. Clade V was subdivided into two subclades, V1 and V2, and clade M comprised one subclade (M1) and 1 genogroup (GrM1). Bootstrap value of more than 80% was observed.</p