Leptochelins A-C, Cytotoxic Metallophores Produced by Geographically Dispersed Strains of Marine Cyanobacteria.

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 .

The Kavaratamides: Discovery of Linear Lipodepsipeptides from the Marine Cyanobacterium Using a Comparative Chemogeographic Analysis.

Kavaratamide A (), a new linear lipodepsipeptide possessing an unusual isopropyl--methylpyrrolinone moiety, was discovered from the tropical marine filamentous cyanobacterium collected from Kavaratti, India. A comparative chemogeographic analysis of . collected from six different geographical regions led to the prioritized isolation of this metabolite from India as distinctive among our data sets.

MHC-Fine: Fine-tuned AlphaFold for precise MHC-peptide complex prediction.

The precise prediction of major histocompatibility complex (MHC)-peptide complex structures is pivotal for understanding cellular immune responses and advancing vaccine design. In this study, we enhanced AlphaFold's capabilities by fine-tuning it with a specialized dataset consisting of exclusively high-resolution class I MHC-peptide crystal structures. This tailored approach aimed to address the generalist nature of AlphaFold's original training, which, while broad-ranging, lacked the granularity necessary for the high-precision demands of class I MHC-peptide interaction prediction.

PECAN Predicts Patterns of Cancer Cell Cytostatic Activity of Natural Products Using Deep Learning.

Many machine learning techniques are used as drug discovery tools with the intent to speed characterization by determining relationships between compound structure and biological function. However, particularly in anticancer drug discovery, these models often make only binary decisions about the biological activity for a narrow scope of drug targets. We present a feed-forward neural network, PECAN (Prediction Engine for the Cytostatic Activity of Natural product-like compounds), that simultaneously classifies the potential antiproliferative activity of compounds against 59 cancer cell lines.

Structure and Biosynthesis of Hectoramide B, a Linear Depsipeptide from Marine Cyanobacterium JHB Discovered via Coculture with .

The tropical marine cyanobacterium JHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies on this strain led to the discovery of several novel compounds such as hectochlorins and jamaicamides. However, bioinformatic analyses of its genome indicate the presence of numerous cryptic biosynthetic gene clusters that have yet to be characterized.

Lake Avernus Has Turned Red: Bioindicator Monitoring Unveils the Secrets of "Gates of Hades".

Lake Avernus is a volcanic lake located in southern Italy. Since ancient times, it has inspired numerous myths and legends due to the occurrence of singular phenomena, such as coloring events. Only recently has an explanation been found for them, i.

MHC-Fine: Fine-tuned AlphaFold for Precise MHC-Peptide Complex Prediction.

The precise prediction of Major Histocompatibility Complex (MHC)-peptide complex structures is pivotal for understanding cellular immune responses and advancing vaccine design. In this study, we enhanced AlphaFold's capabilities by fine-tuning it with a specialized dataset comprised by exclusively high-resolution MHC-peptide crystal structures. This tailored approach aimed to address the generalist nature of AlphaFold's original training, which, while broad-ranging, lacked the granularity necessary for the high-precision demands of MHC-peptide interaction prediction.

Structure and Biosynthesis of Hectoramide B, a Linear Depsipeptide from the Marine Cyanobacterium JHB Discovered via Co-culture with .

The tropical marine cyanobacterium JHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies of this strain led to the discovery of several novel compounds such as the hectochlorins and jamaicamides; however, bioinformatic analyses of its genome suggested that there were many more cryptic biosynthetic gene clusters yet to be characterized. To potentially stimulate the production of novel compounds from this strain, it was co-cultured with .

NPOmix: A machine learning classifier to connect mass spectrometry fragmentation data to biosynthetic gene clusters.

Microbial specialized metabolites are an important source of and inspiration for many pharmaceuticals, biotechnological products and play key roles in ecological processes. Untargeted metabolomics using liquid chromatography coupled with tandem mass spectrometry is an efficient technique to access metabolites from fractions and even environmental crude extracts. Nevertheless, metabolomics is limited in predicting structures or bioactivities for cryptic metabolites.

Development of Potent and Highly Selective Epoxyketone-Based Plasmodium Proteasome Inhibitors.

Here, we present remarkable epoxyketone-based proteasome inhibitors with low nanomolar in vitro potency for blood-stage Plasmodium falciparum and low cytotoxicity for human cells. Our best compound has more than 2,000-fold greater selectivity for erythrocytic-stage P. falciparum over HepG2 and H460 cells, which is largely driven by the accommodation of the parasite proteasome for a D-amino acid in the P3 position and the preference for a difluorobenzyl group in the P1 position.

Discovery of Novel Tyrosinase Inhibitors From Marine Cyanobacteria.

Tyrosinase, an important oxidase involved in the primary immune response in humans, can sometimes become problematic as it can catalyze undesirable oxidation reactions. Therefore, for decades there has been a strong pharmaceutical interest in the discovery of novel inhibitors of this enzyme. Recent studies have also indicated that tyrosinase inhibitors can potentially be used in the treatment of melanoma cancer.

Discovery of pH-Selective Marine and Plant Natural Product Inhibitors of Cathepsin B Revealed by Screening at Acidic and Neutral pH Conditions.

Dysregulation of cathepsin B, which involves the translocation of the enzyme from acidic pH lysosomes to the neutral pH cytosol, followed by the initiation of cell death and inflammation, occurs in numerous brain disorders. The wide difference in the acidic pH (4.6) of lysosomes compared to the neutral pH (7.

Secondary Metabolite Variation and Bioactivities of Two Marine Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS.

Co-culture is known as an efficient way to explore the metabolic potential of fungal strains for new antibiotics and other therapeutic agents that could counter emerging health issues. To study the effect of co-culture on the secondary metabolites and bioactivities of two marine strains, C23-3 and DLEP2008001, they were co-cultured in live or inactivated forms successively or simultaneously. The mycelial morphology and high-performance thin layer chromatography (HPTLC) including bioautography of the fermentation extracts were recorded.

Structure and Candidate Biosynthetic Gene Cluster of a Manumycin-Type Metabolite from .

A new manumycin-type natural product named pacificamide () and its candidate biosynthetic gene cluster () were discovered from the marine actinobacterium CNT-855. The structure of the compound was determined using NMR, electronic circular dichroism, and bioinformatic predictions. The gene cluster is unique to and found in only two of the 119 genomes analyzed across nine species.

Total Synthesis of Laucysteinamide A, a Monomeric Congener of Somocystinamide A.

Laucysteinamide A () is a marine natural product isolated from the cyanobacterium and contains structural motifs found in promising cancer drug leads. The first total synthesis of and its analogues was achieved, which also enabled a concise formal synthesis of somocystinamide A (), a dimeric congener of that previously showed extremely potent antiproliferative activities. This work provides further insights on structure-activity relationships in this class of natural products.

A community resource for paired genomic and metabolomic data mining.

Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.

A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria.

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e.

An anti-inflammatory isoflavone from soybean inoculated with a marine fungus C23-3.

A new isoflavone derivative compound (psoralenone) was isolated from soybean inoculated with a marine fungus C23-3, together with seven known compounds including isoflavones -, butyrolactone I () and blumenol A (). Their structures were elucidated by MS, NMR, and ECD. Psoralenone displayed moderate anti-inflammatory activity in the LPS-induced RAW264.

A Convolutional Neural Network-Based Approach for the Rapid Annotation of Molecularly Diverse Natural Products.

This report describes the first application of the novel NMR-based machine learning tool "Small Molecule Accurate Recognition Technology" (SMART 2.0) for mixture analysis and subsequent accelerated discovery and characterization of new natural products. The concept was applied to the extract of a filamentous marine cyanobacterium known to be a prolific producer of cytotoxic natural products.

Tutuilamides A-C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.

Marine cyanobacteria (blue-green algae) have been shown to possess an enormous capacity to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Using mass-spectrometry-guided fractionation together with molecular networking, cyanobacterial field collections from American Samoa and Palmyra Atoll yielded three new cyclic peptides, tutuilamides A-C. Their structures were established by spectroscopic techniques including 1D and 2D NMR, HR-MS, and chemical derivatization.

Pagoamide A, a Cyclic Depsipeptide Isolated from a Cultured Marine Chlorophyte, sp., Using MS/MS-Based Molecular Networking.

A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (), was isolated from laboratory cultures of a marine Chlorophyte, sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MS-based molecular networking. Cultures were grown in a light- and temperature-controlled environment and harvested after several months of growth.