Roseobacticides: Small Molecule Modulators of an Algal-Bacterial Symbiosis

Marine bacteria and microalgae engage in dynamic symbioses mediated by small molecules. A recent study of <i>Phaeobacter gallaeciensis</i>, a member of the large roseobacter clade of α-proteobacteria, and <i>Emiliania huxleyi</i>, a prominent member of the microphytoplankton found in large algal blooms, revealed that an algal senescence signal produced by <i>E. huxleyi</i> elicits the production of novel algaecides, the roseobacticides, from the bacterial symbiont. In this report, the generality of these findings are examined by expanding the number of potential elicitors. This expansion led to the identification of nine new members of the roseobacticide family, rare bacterial troponoids, which provide insights into both their biological roles and their biosynthesis. The qualitative and quantitative changes in the levels of roseobacticides induced by the additional elicitors and the elicitors’ varied efficiencies support the concept of host-targeted roseobacticide production. Structures of the new family members arise from variable substituents at the C3 and C7 positions of the roseobacticide core as the diversifying elements and suggest that the roseobacticides result from modifications and combinations of aromatic amino acids. Together these studies support a model in which algal senescence converts a mutualistic bacterial symbiont into an opportunistic parasite of its hosts

Antibiotic and Antimalarial Quinones from Fungus-Growing Ant-Associated <i>Pseudonocardia</i> sp.

Three new members of the angucycline class of antibiotics, pseudonocardones A–C (<b>1</b>–<b>3</b>), along with the known antibiotics 6-deoxy-8-<i>O</i>-methylrabelomycin (<b>4</b>) and X-14881 E (<b>5</b>) have been isolated from the culture of a <i>Pseudonocardia</i> strain associated with the fungus-growing ant <i>Apterostigma dentigerum</i>. Compounds <b>4</b> and <b>5</b> showed antibiotic activity against <i>Bacillus subtilis</i> 3610 and liver-stage <i>Plasmodium berghei</i>, while <b>1</b>–<b>3</b> were inactive or only weakly active in a variety of biological assays. Compound <b>5</b> also showed moderate cytotoxicity against HepG2 cells

Sources of Diversity in Bactobolin Biosynthesis by <i>Burkholderia thailandensis</i> E264

A series of deletion mutants in the recently identified bactobolin biosynthetic pathway defined the roles of several key biosynthetic enzymes and showed how promiscuity in three enzyme systems allows this cluster to produce multiple products. Studies on the deletion mutants also led to four new bactobolin analogs that provide additional structure–activity relationships for this interesting antibiotic family

Cystargolides, 20S Proteasome Inhibitors Isolated from <i>Kitasatospora cystarginea</i>

Two novel β-lactone-containing natural products, cystargolides A (<b>1</b>) and B (<b>2</b>), were isolated from the actinomycete <i>Kitasatospora cystarginea</i>. The production of these two natural products was highlighted using a methodology associating liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis and the statistical analysis tool principal component analysis (PCA). Their structures were elucidated by interpretation of NMR experiments and tandem mass spectrometry. The absolute configurations of the amino acid residues were determined using Marfey’s method, and the relative configurations of the β-lactone substituents were determined on the basis of the vicinal ³<i>J</i>_HH coupling value. Due to the presence of the β-lactone, <b>1</b> and <b>2</b> were evaluated for their ability to inhibit the human 20S proteasome. <b>1</b> and <b>2</b> both inhibited the 20S proteasome <i>in vitro</i> with IC₅₀ values of 0.35 and 0.93 μM, respectively

Mixing and Matching Siderophore Clusters: Structure and Biosynthesis of Serratiochelins from <i>Serratia sp.</i> V4

Interrogation of the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophoressoluble, low molecular weight compoundshave an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition to acquire iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of “odd” siderophores can reveal the evolutionary strategy that led to their creation. We report a new <i>Serratia</i> strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well-known siderophore clusters, the <i>Escherichia coli</i> enterobactin cluster and the <i>Vibrio cholera</i> vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores

Microtermolides A and B from Termite-Associated <i>Streptomyces</i> sp. and Structural Revision of Vinylamycin

Microtermolides A (<b>1</b>) and B (<b>2</b>) were isolated from a <i>Streptomyces</i> sp. strain associated with fungus-growing termites. The structures of <b>1</b> and <b>2</b> were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of <b>1</b> led to the re-examination of the structure originally proposed for vinylamycin (<b>3</b>). Based on a comparison of predicted and experimental ¹H and ¹³C NMR chemical shifts, we propose that vinylamycin’s structure be revised from <b>3</b> to <b>4</b>

Hortonones A to C, Hydroazulenones from the Genus <i>Hortonia</i>

The new hexahydroazulenones hortonones A (<b>1</b>) to C (<b>3</b>) were isolated from the leaves of three representative species of the endemic Sri Lankan genus <i>Hortonia</i> that belongs to the family Monimiaceae. Hortonones A (<b>1</b>) and B (<b>2</b>) have the unprecedented rearranged hortonane sesquiterpenoid carbon skeleton, and hortonone C (<b>3</b>) has the unprecedented rearranged and degraded 13-norhortonane skeleton. Hortonone C (<b>3</b>) exhibited in vitro cytotoxicity against human breast cancer MCF-7 cells at 5 μg/mL