Frankobactin Metallophores Produced by Nitrogen-Fixing Frankia Actinobacteria Function in Toxic Metal Sequestration.

A series of new metallophores, referred to as frankobactins, were extracted from cultures of the symbiotic and nitrogen-fixing actinobacterium Frankia sp. CH37. Structure elucidation revealed a 2-hydroxyphenyl-substituted oxazoline core and a chain composed of five proteinogenic and nonproteinogenic amino acids, suggesting nonribosomal peptide synthesis as the biosynthetic origin. By whole-genome sequencing, bioinformatic analysis, and comparison with other Frankia strains, the genetic locus responsible for the biosynthesis was detected. Spectrophotometric titration of frankobactin with Fe(III) and Cu(II) and mass spectrometry established the 1:1 (metal:frankobactin) coordination. Uptake experiments suggested that frankobactin A1 (1) did not serve to recruit iron, but to detoxify Cu(II). As frankobactin A1 prevents the cellular entry of Cu(II), it could play a crucial role in the symbiosis of Frankia sp. and its host in the reclamation of copper-contaminated soil.

Correction: A genomics perspective on natural product biosynthesis in plant pathogenic bacteria.

Correction for 'A genomics perspective on natural product biosynthesis in plant pathogenic bacteria' by Florian Baldeweg et al., Nat. Prod. Rep., 2019, 36, 307-325.

Simultaneous Production of Psilocybin and a Cocktail of ß-Carboline Monoamine Oxidase Inhibitors in "Magic" Mushrooms.

The psychotropic effects of Psilocybe "magic" mushrooms are caused by the l-tryptophan-derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other l-tryptophan-derived ß-carbolines as their natural products, which was confirmed by 1D and 2D NMR spectroscopy. Stable-isotope labeling with 13 C11 -l-tryptophan verified the ß-carbolines as biosynthetic products of these fungi. In addition, MALDI-MS imaging showed that ß-carbolines accumulate toward the hyphal apices. As potent inhibitors of monoamine oxidases, ß-carbolines are neuroactive compounds and interfere with psilocybin degradation. Therefore, our findings represent an unprecedented scenario of natural product pathways that diverge from the same building block and produce dissimilar compounds, yet contribute directly or indirectly to the same pharmacological effects.

A genomics perspective on natural product biosynthesis in plant pathogenic bacteria.

Covering: up to February 2018 In recent years, genome sequencing revealed the full biosynthetic potential of bacteria causing plant diseases. Bioinformatics and advanced analytical techniques paved the way to clarify the structures of long-sought natural products with a role in virulence. Furthermore, several compounds without disease-associated function were discovered. The exploration of these molecules disclosed persistence strategies of plant pathogenic bacteria outside their hosts and provided access to new bioactive compounds with therapeutic potential. In this review, we will summarize some of the striking findings in the field, paying particular attention to unique natural product pathways and their unprecedented biosynthetic features as well as the biological activities of the retrieved compounds.

Biocatalytic Production of Psilocybin and Derivatives in Tryptophan Synthase-Enhanced Reactions.

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the main alkaloid of the fungal genus Psilocybe, the so-called "magic mushrooms." The pharmaceutical interest in this psychotropic natural product as a future medication to treat depression and anxiety is strongly re-emerging. Here, we present an enhanced enzymatic route of psilocybin production by adding TrpB, the tryptophan synthase of the mushroom Psilocybe cubensis, to the reaction. We capitalized on its substrate flexibility and show psilocybin formation from 4-hydroxyindole and l-serine, which are less cost-intensive substrates, compared to the previous method. Furthermore, we show enzymatic production of 7-phosphoryloxytryptamine (isonorbaeocystin), a non-natural congener of the Psilocybe alkaloid norbaeocystin (4-phosphoryloxytryptamine), and of serotonin (5-hydroxytryptamine) by means of the same in vitro approach.

Fungal Biosurfactants from Mortierella alpina.

The zygomycete Mortierella alpina is a well-known producer of polyunsaturated fatty acids in the food industry. Two series of its secondary metabolites are reported: Malpinins, a family of amphiphilic acetylated hexapeptides, were chemically characterized and serve as natural emulsifiers during lipid secretion. Additionally, hydrophobic cyclopentapeptides, malpibaldins, were structurally elucidated by NMR experiments, and their absolute stereochemistry was elucidated through chemical derivatization and synthesis. This work highlights lower fungi as a novel reservoir for natural products.

Cross-Chemistry Leads to Product Diversity from Atromentin Synthetases in Aspergilli from Section Nigri.

Non-ribosomal peptide synthetase (NRPS)-like enzymes catalyze the non-oxidative homodimerization of aromatic α-keto acids, but the exact reaction mechanism is unknown. The furanone-forming thioesterase domain of the Aspergillus terreus aspulvinone E synthetase MelA displays a predicted quinone-forming motif, whereby its catalytic triad contains an essential cysteine indicating an unusual thioester intermediate. To convert MelA into a quinone-forming atromentin synthetase its thioesterase domain was replaced with that from a Paxillus involutus or A. terreus atromentin synthetase. Phylogenetic proximity of donor and acceptor seems important, as only replacement with the A. terreus thioesterase was functional. Heterologous expression of atromentin synthetases in Aspergillus niger and Aspergillus oryzae revealed host-dependent product formation whereby cross-chemistry directed atromentin biosynthesis in A. niger toward atrofuranic acid. Screening of aspergilli from section Nigri identified an atromentin synthetase in Aspergillus brasiliensis that produced atrofuranic acid in the homologous host. Therefore, cross-chemistry on quinone cores appears common to section Nigri.

Structure of Ralsolamycin, the Interkingdom Morphogen from the Crop Plant Pathogen Ralstonia solanacearum.

Ralsolamycin, an inducer of chlamydospore formation in fungi, was recently reported from the plant pathogenic bacterium Ralstonia solanacearum. Although interpretation of tandem mass data and bioinformatics enabled a preliminary chemical characterization, the full structure of ralsolamycin was not resolved. We now report the recovery of this secondary metabolite from an engineered R. solanacearum strain. The structure of ralsolamycin was elucidated by extensive spectroscopic analyses. Chemical derivatization as well as bioinformatics were used to assign the absolute stereochemistry. Our results identified an erroneous genome sequence, thereby emphasizing the value of chemical methods to complement bioinformatics-based procedures in natural product research.