Covering: 1992 to 2024Type-I polyketide synthase (PKS)-derived metabolites are structurally diverse bioactive natural products containing multiple stereogenic centres. This review focuses on the configurational analysis of type-I PKS-derived natural products, emphasizing the methodologies and challenges associated with determining their stereochemistry due to their complex structures with multiple chiral centres. Key strategies include <i>J</i>-based configuration analysis (JBCA), chemical derivatizations with chiral reagents, degradation methods, NMR spectroscopic analysis, and the exploitation of chiroptical properties. Case studies demonstrate the practical applications of these methods in elucidating the stereochemistry of type-I polyketide natural products.

Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus <i>Leptothoe</i>. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three <i>Leptothoe</i> strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.

The Maillard reaction, known as the condensation of reduced sugars with amino acids, can be a great source of pyrroles for the discovery of bioactive compounds. In the present study, using glucose and l-alanine, two new pyrrolopyrazinones (<b>1a</b> and <b>1b</b>) were obtained. Subsequently, two more new pyrrolopyrazinones (<b>2a</b> and <b>2b</b>) were prepared by further hydrolyzing the methyl ester into carboxylic acid. The structures of the pyrrolopyrazinones were determined by interpretation of 1D and 2D NMR and HRESIMS data as well as computational calculation of ECD Cotton effects. Moreover, the broad ¹H NMR peak shapes observed in the pyrrolopyrazinones were accurately resolved to the presence of long-range couplings, including allylic ⁴ <i>J</i> and homoallylic ⁵ <i>J</i> couplings, by employing quantum mechanics-driven ¹H iterative full spin analysis (QM-HiFSA). The four pyrrolopyrazinones were evaluated for their biological efficacy in the treatment of diabetes in terms of their structural elements, including carboxyl functional groups. As a result, all four compounds were found to be moderately effective in inhibiting aldose reductase and also in proliferating mesenchymal stem cells.

The Antarctic marine environment is a promising region for the discovery of extraordinary microbial taxa and the exploration of their applications. This study aimed to investigate the phylogenetic diversity of culturable actinomycetes from deep sea bottom sediment of the Amundsen Sea, Antarctica, and their potential to produce novel metabolites. A total of 24 actinomycete strains were isolated and assigned to the following genera based on the 16S rRNA gene sequence analysis: Blastococcus (3 strains), Corynebacterium (2 strains), Microbacterium (3 strains), Micrococcus (1 strain), Modestobacter (3 strains), Nocardioides (3 strains), Rhodococcus (6 stains), and Streptomyces (3 strains). The 15 strains were selected and chemically investigated. A molecular networking analysis was performed using tandem mass spectrometry (MS/MS) to analyze the metabolites produced by 15 strains. This analysis was used to annotate known compounds and identify potential novel compounds. The molecular network that resulted from this analysis contained 3,702 parent ions. Of these, 1,414 parent ions (38.20%) were identified as genus-specific compounds. Feature-based molecular networking analysis revealed the presence of 269 annotated compounds within the GNPS library. This study demonstrates the diversity of the marine actinomycetes isolated from Amundsen Sea sediment. Additionally, the molecular networking analysis suggests the capacity for the production of biologically active compounds.

Covering: 1992 to 2024Type-I polyketide synthase (PKS)-derived metabolites are structurally diverse bioactive natural products containing multiple stereogenic centres. This review focuses on the configurational analysis of type-I PKS-derived natural products, emphasizing the methodologies and challenges associated with determining their stereochemistry due to their complex structures with multiple chiral centres. Key strategies include <i>J</i>-based configuration analysis (JBCA), chemical derivatizations with chiral reagents, degradation methods, NMR spectroscopic analysis, and the exploitation of chiroptical properties. Case studies demonstrate the practical applications of these methods in elucidating the stereochemistry of type-I polyketide natural products.

Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus <i>Leptothoe</i>. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three <i>Leptothoe</i> strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.