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Chemosphere Jun 2024Polyhydroxyalkanoates (PHAs) are important candidates for replacing petroleum-based plastics. This transition is urgent for the development of a biobased economy and to...
Polyhydroxyalkanoates (PHAs) are important candidates for replacing petroleum-based plastics. This transition is urgent for the development of a biobased economy and to protect human health and natural ecosystems. PHAs are biobased and biodegradable polyesters that when blended with other polymers, such as poly(butylene adipate-co-terephthalate) (PBAT), acquire remarkable improvements in their properties, which allow them to comply with the requirements of packaging applications. However, the biodegradation of such blends should be tested to evaluate the impact of those polymers in the environment. For instance, PBAT is a compostable aliphatic-aromatic copolyester, and its biodegradation in natural environments, such as soil, is poorly studied. In this work, we evaluated the biodegradation of a bilayer film composed of PHB and PBAT, by a soil microbiome. The bilayer film reached 47 ± 1 % mineralization in 180 days and PHB was no longer detected after this period. The increased crystallinity of the PBAT residue was a clear sign of biodegradation, indicating that the amorphous regions were preferentially biodegraded. Seven microorganisms were isolated, from which 4 were closely related to microorganisms already known as PHB degraders, but the other 3 species, closely related to Streptomyces coelicoflavus, Clonostachys rosea and Aspergillus insuetus, were found for the first time as PHB degraders. Most remarkably, two fungi closely related to Purpureocillium lilacinum and Aspergillus pseudodeflectus (99.83 % and 100 % identity by ITS sequencing) were isolated and identified as PBAT degraders. This is very interesting due to the rarity of isolating PBAT-degrading microorganisms. These results show that the bilayer film can be biodegraded in soil, at mesophilic temperatures, showing its potential to replace synthetic plastics in food packaging.
PubMed: 38925517
DOI: 10.1016/j.chemosphere.2024.142696 -
The FEBS Journal Jun 2024Polyketides are natural products synthesized by polyketide synthases (PKSs), where acyltransferase (AT) domains play a crucial role in selection of extender units....
Polyketides are natural products synthesized by polyketide synthases (PKSs), where acyltransferase (AT) domains play a crucial role in selection of extender units. Engineering of AT domains enables the site-specific incorporation of non-natural extender units, leading to generation of novel derivatives. Here, we determined the crystal structures of AT domains from the fifth module of tylosin PKS (TylAT5) derived from Streptomyces fradiae and the eighth module of spinosad PKS (SpnAT8) derived from Saccharopolyspora spinosa, and combined them with molecular dynamics simulations and enzyme kinetic studies to elucidate the molecular basis of substrate selection. The ethylmalonyl-CoA-specific conserved motif TAGH of TylAT5 and the MMCoA-specific conserved motif YASH of SpnAT8 were identified within the substrate-binding pocket, and several key residues close to the substrate acyl moiety were located. Through site-directed mutagenesis of four residues near the active site, we successfully reprogrammed the specificity of these two AT domains toward malonyl-CoA. Mutations in TylAT5 enhanced its catalytic activity 2.6-fold toward malonyl-CoA, and mutations in SpnAT8 eliminated the substrate promiscuity. These results extend our understanding of AT substrate specificity and would benefit the engineering of PKSs.
PubMed: 38922792
DOI: 10.1111/febs.17206 -
Toxins May 2024Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field...
Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field application of microorganisms to degrade and detoxify ZEN is a promising strategy to enhance the safety of food and feed. In this study, we investigated the potential of three actinobacterial strains to degrade and detoxify ZEN in vitro and in planta on wheat ears. The residual ZEN concentration and toxicity in the samples were analysed with UHPLC-MS/MS and a bioluminescence BLYES assay, respectively. subsp. LMG19352 could completely degrade and detoxify 5 mg/L ZEN in LB broth within 24 h, along with significant reductions in ZEN concentration both in a minimal medium (MM) and on wheat ears. Additionally, it was the only strain that showed a significant colonisation of these ears. sp. R25614 exhibited partial but significant degradation in LB broth and MM, whereas sp. LMG16995 degraded and detoxified ZEN in LB broth after 72 h by 39% and 33%, respectively. Although all three actinobacterial strains demonstrated the metabolic capability to degrade and detoxify ZEN in vitro, only subsp. LMG19352 showed promising potential to mitigate ZEN in planta. This distinction underscores the importance of incorporating in planta screening assays for assessing the potential of mycotoxin-biotransforming microorganisms as biocontrol agents.
Topics: Zearalenone; Triticum; Biological Control Agents; Streptomyces; Actinobacteria; Food Contamination; Tandem Mass Spectrometry
PubMed: 38922147
DOI: 10.3390/toxins16060253 -
Marine Drugs Jun 2024Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of...
Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of deepsea-derived SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains CCARM 5172 and CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 μg/mL.
Topics: Streptomyces; Lipopeptides; Microbial Sensitivity Tests; Anti-Bacterial Agents; Enterococcus faecalis; Peptides, Cyclic; Enterococcus faecium; Drug Resistance, Multiple, Bacterial; Bacterial Proteins
PubMed: 38921573
DOI: 10.3390/md22060262 -
Marine Drugs Jun 2024A new dimeric C-glycoside polyketide chrysomycin F (), along with four new monomeric compounds, chrysomycins G (), H (), I (), J (), as well as three known analogues,...
A new dimeric C-glycoside polyketide chrysomycin F (), along with four new monomeric compounds, chrysomycins G (), H (), I (), J (), as well as three known analogues, chrysomycins A (), B (), and C (), were isolated and characterised from a strain of sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type and a number of clinically isolated MDR strains.
Topics: Streptomyces; Mycobacterium tuberculosis; Antitubercular Agents; Polyketides; Microbial Sensitivity Tests; Glycosides; China; Molecular Structure; Anthraquinones
PubMed: 38921570
DOI: 10.3390/md22060259 -
Marine Drugs May 2024Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new...
Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (-), along with the known analogue coelomycin (), as well as a new azaphilone, noonaphilone A (). Structures were assigned to - on the basis of a detailed spectroscopic analysis, and in the case of -, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for -, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, incorporates a rare -Tyr motif, typically only reported in a limited array of metabolites. Similarly, a plausible biosynthetic pathway is proposed for , highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7 noonaphilone A () versus the 7 deflectin 1a ().
Topics: Aspergillus; Australia; Diketopiperazines; Aquatic Organisms; Biosynthetic Pathways; Crystallography, X-Ray; Molecular Structure; Benzopyrans; Pigments, Biological
PubMed: 38921553
DOI: 10.3390/md22060243 -
Organic & Biomolecular Chemistry Jun 2024Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective...
Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective synthesis of all stereoisomers of geosmin is reported, yielding all compounds in high enantiomeric purity. Furthermore, the stereoselective synthesis of a geosmin derivative isolated from a mangrove associated streptomycete was performed, establishing the absolute configuration of the natural product. Finally, a new side product of the geosmin synthase from was isolated and its structure was elucidated by NMR spectroscopy. The absolute configuration of this new compound was determined through a stereoselective synthesis.
PubMed: 38920404
DOI: 10.1039/d4ob00934g -
Journal of Agricultural and Food... Jun 2024Validamycin A (VMA) is an antifungal antibiotic derived from commonly used in plant disease management. Surprisingly, VMA was discovered to impede the production of...
Validamycin A (VMA) is an antifungal antibiotic derived from commonly used in plant disease management. Surprisingly, VMA was discovered to impede the production of fumonisin B1 (FB) in agricultural settings. However, the specific target of VMA in remained unclear. To unravel the molecular mechanism of VMA, ultrastructural observations unveiled damage to mitochondrial membranes. Trehalase (FvNth) was pinpointed as the target of VMA by utilizing a 3D-printed surface plasmon resonance sensor. Molecular docking identified Trp, Arg, Asp, and Phe as the binding sites between VMA and FvNth. A mutant lacking amino acids 250-670 was engineered through homologous recombination. Transcriptome analysis indicated that samples treated with VMA and displayed similar expression patterns, particularly in the suppression of the FUM gene cluster. VMA treatment resulted in reduced trehalase and ATPase activity as well as diminished production of glucose, pyruvic acid, and acetyl-CoA. Conversely, these effects were absent in samples treated with . This research proposes that VMA hinders acetyl-CoA synthesis by trehalase, thereby suppressing the FB biosynthesis. These findings present a novel target for the development of mycotoxin control agents.
PubMed: 38917402
DOI: 10.1021/acs.jafc.4c02641 -
NAR Genomics and Bioinformatics Jun 2024Microbial specialized metabolite biosynthetic gene clusters (SMBGCs) are a formidable source of natural products of pharmaceutical interest. With the multiplication of...
Microbial specialized metabolite biosynthetic gene clusters (SMBGCs) are a formidable source of natural products of pharmaceutical interest. With the multiplication of genomic data available, very efficient bioinformatic tools for automatic SMBGC detection have been developed. Nevertheless, most of these tools identify SMBGCs based on sequence similarity with enzymes typically involved in specialised metabolism and thus may miss SMBGCs coding for undercharacterised enzymes. Here we present Synteruptor (https://bioi2.i2bc.paris-saclay.fr/synteruptor), a program that identifies genomic islands, known to be enriched in SMBGCs, in the genomes of closely related species. With this tool, we identified a SMBGC in the genome of ATCC23877, undetected by antiSMASH versions prior to antiSMASH 5, and experimentally demonstrated that it directs the biosynthesis of two metabolites, one of which was identified as sphydrofuran. Synteruptor is also a valuable resource for the delineation of individual SMBGCs within antiSMASH regions that may encompass multiple clusters, and for refining the boundaries of these SMBGCs.
PubMed: 38915823
DOI: 10.1093/nargab/lqae069 -
The Journal of Antibiotics Jun 2024Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces...
Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.
PubMed: 38914796
DOI: 10.1038/s41429-024-00754-y