Marine cyanobacteria are a rich source of complex bioactive secondary metabolites which derive from mixed biosynthetic pathways. Recently, several marine cyanobacterial natural products have garnered much attention due to their intriguing structures and exciting anti-proliferative or cancer cell toxic activities. Several other recently discovered secondary metabolites exhibit insightful neurotoxic activities whereas others are showing pronounced anti-inflammatory activity. A number of anti-infective compounds displaying activity against neglected diseases have also been identified, which include viridamides A and B, gallinamide A, dragonamide E, and the almiramides.

Assignment of complex molecular structures from nuclear magnetic resonance (NMR) data can be prone to interpretational mistakes. Residual dipolar couplings (RDCs) and residual chemical shift anisotropy (RCSA) provide a spatial view of the relative orientations between bonds and chemical shift shielding tensors respectively, regardless of separation. Consequently, these data constitute an excellent reporter of global structural validity. Anisotropic NMR parameters can be used to evaluate investigators’ structure proposals or structures generated by Computer-Aided Structure Elucidation (CASE). Application of the method to several complex structure assignment problems shows promising results that signal a potential paradigm shift from conventional NMR data interpretation, of particular utility for compounds not amenable to x-ray crystallography.

Microbes sense and respond to their environment with small molecules, and discovering these molecules and identifying their functions informs chemistry, biology, and medicine. As part of a study of molecular exchanges between termite-associated actinobacteria and pathogenic fungi, we uncovered a remarkable fungal metabolite, homodimericin A, which is strongly upregulated by the bacterial metabolite bafilomycin C1. Homodimericin A is a hexacyclic polyketide with a carbon backbone containing eight contiguous stereogenic carbons in a C20 hexacyclic core. Only half of its carbon atoms have an attached hydrogen, which presented a significant challenge for NMR-based structural analysis. In spite of its microbial production and rich stereochemistry, homodimericin A occurs naturally as a racemic mixture. A plausible nonenzymatic reaction cascade leading from two identical achiral monomers to homodimericin A is presented, and homodimericin A’s formation by this path, a six-electron oxidation, could be a response to oxidative stress triggered by bafilomycin C1.

Some anaerobic bacteria use insoluble minerals as terminal electron acceptors and discovering the ways in which electrons move through the membrane barrier to the exterior acceptor forms an active field of research with implications for both bacterial physiology and bioenergy. A previous study suggested that Shewanella oneidensis MR-1 utilizes a small, polar, redox active molecule that serves as an electron shuttle between the bacteria and insoluble acceptors, but the shuttle itself has never been identified. Through isolation and synthesis, we identify it as ACNQ (2-amino-3-carboxy-1,4-naphthoquinone), a soluble analog of menaquinone. ACNQ is derived from DHNA (1,4-dihydroxy-2-naphthoic acid) in a non-enzymatic process that frustrated genetic approaches to identify the shuttle. Both ACNQ and DHNA restore reduction of AQDS under anaerobic growth in menaquinone-deficient mutants. Bioelectrochemistry analyses reveal that ACNQ (−0.32 VAg/AgCl) contributes to the extracellular electron transfer (EET) as an electron shuttle, without altering menaquinone generation or EET related cytochrome c expression.