Metabolomics and Genomics Enable the Discovery of a New Class of Nonribosomal Peptidic Metallophores from a Marine Micromonospora.

Although microbial genomes harbor an abundance of biosynthetic gene clusters, there remain substantial technological gaps that impair the direct correlation of newly discovered gene clusters and their corresponding secondary metabolite products. As an example of one approach designed to minimize or bridge such gaps, we employed hierarchical clustering analysis and principal component analysis (hcapca, whose sole input is MS data) to prioritize 109 marine Micromonospora strains and ultimately identify novel strain WMMB482 as a candidate for in-depth "metabologenomics" analysis following its prioritization. Highlighting the power of current MS-based technologies, not only did hcapca enable the discovery of one new, nonribosomal peptide bearing an incredible diversity of unique functional groups, but metabolomics for WMMB482 unveiled 16 additional congeners via the application of Global Natural Product Social molecular networking (GNPS), herein named ecteinamines A-Q (1-17). The ecteinamines possess an unprecedented skeleton housing a host of uncommon functionalities including a menaquinone pathway-derived 2-naphthoate moiety, 4-methyloxazoline, the first example of a naturally occurring Ψ[CH2NH] "reduced amide", a methylsulfinyl moiety, and a d-cysteinyl residue that appears to derive from a unique noncanonical epimerase domain. Extensive in silico analysis of the ecteinamine (ect) biosynthetic gene cluster and stable isotope-feeding experiments helped illuminate the novel enzymology driving ecteinamine assembly as well the role of cluster collaborations or "duets" in producing such structurally complex agents. Finally, ecteinamines were found to bind nickel, cobalt, zinc, and copper, suggesting a possible biological role as broad-spectrum metallophores.

Rapid Unambiguous Structure Elucidation of Streptnatamide A, a New Cyclic Peptide Isolated from A Marine-derived Streptomyces sp.

Cyclic peptides have been excellent source of drug leads. With the advances in discovery platforms, the pharmaceutical industry has a growing interest in cyclic peptides and has pushed several into clinical trials. However, structural complexity of cyclic peptides brings extreme challenges for structure elucidation efforts. Isotopic fine structure analysis, Nuclear magnetic resonance (NMR), and detailed tandem mass spectrometry rapidly provided peptide sequence for streptnatamide A, a cyclic peptide isolated from a marine-derived Streptomyces sp. Marfey's analysis determined the stereochemistry of all amino acids, enabling the unambiguous structure determination of this compound. A non-ribosomal peptide synthetase biosynthetic gene cluster (stp) was tentatively identified and annotated for streptnatamide A based on the in silico analysis of whole genome sequencing data. These analytical tools will be powerful tools to overcome the challenges for cyclic peptide structure elucidation and accelerate the development of bioactive cyclic peptides.

Bacillibactins E and F from a Marine Sponge-Associated Bacillus sp.

Chemical investigation of a marine sponge-associated Bacillus sp. led to the discovery of bacillibactins E and F (1 and 2). Despite containing the well-established cyclic triester core of iron-binding natural products such as enterobactin, bacillibactins E and F (1 and 2) are the first bacterial siderophores that contain nicotinic and benzoic acid moieties. The structures of the new compounds, including their absolute configurations, were determined by extensive spectroscopic analyses and Marfey's method. A plausible biosynthetic pathway to 1 and 2 is proposed; this route bears great similarity to other previously established bacillibactin-like pathways but appears to differentiate itself by a promiscuous DhbE, which likely installs the nicotinic moiety of 1 and the benzoic acid group of 2.

Nanofiber-Directed Anisotropic Self-Assembly of CdSe-CdS Quantum Rods for Linearly Polarized Light Emission Evidenced by Quantum Rod Orientation Microscopy.

Hybrid soft materials composed of CdSe-CdS nanorods or "quantum rods" (QRs) and the fluorescent 2,3-didecyloxyanthracene (DDOA) low molecular weight organogelator are obtained through self-assembly. Spectroscopy, microscopy, and rheology studies show that the QRs and DDOA coassemble, thereby stabilizing the organogels. Depending on the QR load and excitation wavelength, single nanofibers (NFs) of the hybrid gel display either sharp polarized red luminescence (under green excitation), or dual perpendicularly polarized blue and red emissions (under UV excitation). Transmission electron microscopy, microspectroscopy, and quantum rod orientation microscopy (QROM) reveal that QRs align along the organogel NFs with order parameters reaching 76% and 87%. This paves the way for obtaining surfaces of QR/NF assemblies yielding sharp red linearly polarized emission. In addition, this work demonstrates that QRs can be used more generally to probe nanostructured soft materials, even nonemissive ones. QROM allows to establish maps of the orientation of single QRs dispersed onto or within a gel network by measuring the polarization of the emission of the individual QRs. As occurs within this work in which QRs and NFs interact, the orientation of each QR reveals information on the underlying nanostructure (such as surface striation, bundle formation, and helicity).

Synthesis of aryl sulfides via radical-radical cross coupling of electron-rich arenes using visible light photoredox catalysis.

Electron-rich arenes react with aryl and alkyl disulfides in the presence of catalytic amounts of [Ir(dF(CF3)ppy)2(dtbpy)]PF6 and (NH4)2S2O8 under blue light irradiation to yield arylthiols. The reaction proceeds at room temperature and avoids the use of prefunctionalized arenes. Experimental evidence suggests a radical-radical cross coupling mechanism.

Photocatalytic carbanion generation - benzylation of aliphatic aldehydes to secondary alcohols.

We present a redox-neutral method for the photocatalytic generation of carbanions. Benzylic carboxylates are photooxidized by single electron transfer; immediate CO2 extrusion and reduction of the in situ formed radical yields a carbanion capable of reacting with aliphatic aldehydes as electrophiles giving the Grignard analogous reaction product.

Metallogels of indium(iii) with bile salts: soft materials for nanostructured In2S3 synthesis.

This work describes sonication mediated facile metallo-hydrogel formation from biodetergents sodium cholate and deoxycholate in the presence of indium(iii). The resulting thermo-irreversible gels behaved as viscoelastic soft solids as observed by rheological measurements. Scanning electron and atomic force microscopy analysis revealed the transition from spherical aggregates before gelation to typical entangled three-dimensional fibrous networks in gels. The In-Ch hydrogel was further used to prepare nanostructured In2S3 in which the cholate units acted as surfactants to limit the growth of the nanoflakes.