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1.
J Am Chem Soc ; 146(29): 20370-20378, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38981108

RESUMO

The antibiotic cerulenin is a fungal natural product identified as a covalent inhibitor of ketosynthases within fatty acid and polyketide biosynthesis. Due to its selective and potent inhibitory activity, cerulenin has found significant utility in multidisciplinary biochemical, biomedical, and clinical studies. Although its covalent inhibition profile has been confirmed, cerulenin's mechanism has not been fully determined at a molecular level, frustrating the drug development of related analogues. Herein, we describe the use of stable isotopic tracking with NMR and MS methods to unravel the covalent mechanism of cerulenin against type II fatty acid ketosynthases. We detail the discovery of a unique C2-C3 retro-aldol bond cleavage and a structural rearrangement upon covalent inhibition of cerulenin at the active cysteine residue in E. coli type II fatty acid ketosynthases FabB and FabF.


Assuntos
Cerulenina , Cerulenina/farmacologia , Cerulenina/química , Escherichia coli/enzimologia , Escherichia coli/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Ácido Graxo Sintase Tipo II/antagonistas & inibidores , Ácido Graxo Sintase Tipo II/metabolismo , Modelos Moleculares , Estrutura Molecular
2.
ACS Chem Biol ; 19(7): 1416-1425, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38909314

RESUMO

Carrier proteins (CPs) play a fundamental role in the biosynthesis of fatty acids, polyketides, and non-ribosomal peptides, encompassing many medicinally and pharmacologically relevant compounds. Current approaches to analyze novel carrier-protein-dependent synthetic pathways are hampered by a lack of activity-based assays for natural product biosynthesis. To fill this gap, we turned to 3-methoxychromones, highly solvatochromic fluorescent molecules whose emission intensity and wavelength are heavily dependent on their immediate molecular environment. We have developed a solvatochromic carrier-protein-targeting probe which is able to selectively fluoresce when bound to a target carrier protein. Additionally, the probe displays distinct responses upon CP binding in carrier-protein-dependent synthases. This discerning approach demonstrates the design of solvatochromic fluorophores with the ability to identify biosynthetically active CP-enzyme interactions.


Assuntos
Corantes Fluorescentes , Corantes Fluorescentes/química , Proteínas de Transporte/metabolismo , Proteínas de Transporte/química , Fluorometria/métodos , Panteteína/análogos & derivados , Panteteína/metabolismo , Panteteína/química
3.
J Am Chem Soc ; 146(27): 18650-18660, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38875499

RESUMO

The acyl carrier protein of Escherichia coli, termed AcpP, is a prototypical example of type II fatty acid synthase systems found in many bacteria. It serves as a central hub by accepting diverse acyl moieties (4-18 carbons) and shuttling them between its multiple enzymatic partners to generate fatty acids. Prior structures of acyl-AcpPs established that thioester-linked acyl cargos are sequestered within AcpP's hydrophobic lumen. In contrast, structures of enzyme-bound acyl-AcpPs showed translocation of AcpP-tethered acyl chains into the active sites of enzymes. The mechanistic underpinnings of this conformational interplay, termed chain-flipping, are unclear. Here, using heteronuclear NMR spectroscopy, we reveal that AcpP-tethered acyl chains (6-10 carbons) spontaneously adopt lowly populated solvent-exposed conformations. To this end, we devised a new strategy to replace AcpP's thioester linkages with 15N-labeled amide bonds, which facilitated direct "visualization" of these excited states using NMR chemical exchange saturation transfer and relaxation dispersion measurements. Global fitting of the corresponding data yielded kinetic rate constants of the underlying equilibrium and populations and lifetimes of solvent-exposed states. The latter were influenced by acyl chain composition and ranged from milliseconds to submilliseconds for chains containing six, eight, and ten carbons, owing to their variable interactions with AcpP's hydrophobic core. Although transient, the exposure of AcpP-tethered acyl chains to the solvent may allow relevant enzymes to gain access to its active thioester, and the enzyme-induced selection of this conformation will culminate in the production of fatty acids.


Assuntos
Proteína de Transporte de Acila , Proteínas de Escherichia coli , Escherichia coli , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Escherichia coli/enzimologia , Escherichia coli/química , Proteína de Transporte de Acila/química , Proteína de Transporte de Acila/metabolismo , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Ácido Graxo Sintase Tipo II
4.
Sci Rep ; 14(1): 6036, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472254

RESUMO

The accumulation of microplastics in various ecosystems has now been well documented and recent evidence suggests detrimental effects on various biological processes due to this pollution. Accumulation of microplastics in the natural environment is ultimately due to the chemical nature of widely used petroleum-based plastic polymers, which typically are inaccessible to biological processing. One way to mitigate this crisis is adoption of plastics that biodegrade if released into natural environments. In this work, we generated microplastic particles from a bio-based, biodegradable thermoplastic polyurethane (TPU-FC1) and demonstrated their rapid biodegradation via direct visualization and respirometry. Furthermore, we isolated multiple bacterial strains capable of using TPU-FC1 as a sole carbon source and characterized their depolymerization products. To visualize biodegradation of TPU materials as real-world products, we generated TPU-coated cotton fabric and an injection molded phone case and documented biodegradation by direct visualization and scanning electron microscopy (SEM), both of which indicated clear structural degradation of these materials and significant biofilm formation.


Assuntos
Plásticos , Poliuretanos , Plásticos/química , Poliuretanos/química , Microplásticos , Ecossistema , Biodegradação Ambiental
5.
J Am Chem Soc ; 146(2): 1388-1395, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38176024

RESUMO

Site-specific covalent conjugation offers a powerful tool to identify and understand protein-protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coli acyl carrier protein (AcpP) with its partner BioF, a key pyridoxal 5'-phosphate (PLP)-dependent enzyme in the early steps of biotin biosynthesis by targeting a tyrosine residue proximal to the active site. We identify the site of crosslink by MS/MS analysis of the peptide originating from both partners. We further evaluate the BioF-AcpP interface through protein crystallography and mutational studies. Among the AcpP-interacting BioF surface residues, three critical arginine residues appear to be involved in AcpP recognition so that pimeloyl-AcpP can serve as the acyl donor for PLP-mediated catalysis. These findings validate an evolutionary gain-of-function for BioF, allowing the organism to build biotin directly from fatty acid biosynthesis through surface modifications selective for salt bridge formation with acidic AcpP residues.


Assuntos
Biotina , Fluoretos , Compostos de Enxofre , Espectrometria de Massas em Tandem , Biotina/metabolismo , Escherichia coli/metabolismo , Ácidos Graxos/metabolismo
6.
Biochemistry ; 62(24): 3548-3553, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38039071

RESUMO

Outside of their involvement in energy production, mitochondria play a critical role for the cell through their access to a discrete pathway for fatty acid biosynthesis. Despite decades of study in bacterial fatty acid synthases (the putative evolutionary mitochondrial precursor), our understanding of human mitochondrial fatty acid biosynthesis remains incomplete. In particular, the role of the key carrier protein, human mitochondrial acyl carrier protein (mACP), which shuttles the substrate intermediates through the pathway, has not been well-studied in part due to challenges in protein expression and purification. Herein, we report a reliable method for recombinant Escherichia coli expression and purification of mACP. Fundamental characteristics, including substrate sequestration and chain-flipping activity, are demonstrated in mACP using solvatochromic response. This study provides an efficient approach toward understanding the fundamental protein-protein interactions of mACP and its partner proteins, ultimately leading to a molecular understanding of human mitochondrial diseases such as mitochondrial fatty acid oxidation deficiencies.


Assuntos
Proteína de Transporte de Acila , Ácidos Graxos , Humanos , Proteína de Transporte de Acila/metabolismo , Escherichia coli/metabolismo , Ácido Graxo Sintases/química , Ácidos Graxos/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo
7.
Chem Sci ; 14(39): 10925-10933, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37829009

RESUMO

Protein-reactive natural products such as the fungal metabolite cerulenin are recognized for their value as therapeutic candidates, due to their ability to selectively react with catalytic residues within a protein active site or a complex of protein domains. Here, we explore the development of fatty-acid and polyketide-synthase probes by synthetically modulating cerulenin's functional moieties. Using a mechanism-based approach, we reveal unique reactivity within cerulenin and adapt it for fluorescent labeling and crosslinking of fatty-acid and iterative type-I polyketide synthases. We also describe two new classes of silylcyanohydrin and silylhemiaminal masked crosslinking probes that serve as new tools for activity and structure studies of these biosynthetic pathways.

8.
ACS Chem Biol ; 18(9): 2014-2022, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37671411

RESUMO

Carrier-protein-dependent metabolic pathways biosynthesize fatty acids, polyketides, and non-ribosomal peptides, producing metabolites with important pharmaceutical, environmental, and industrial properties. Recent findings demonstrate that these pathways rely on selective communication mechanisms involving protein-protein interactions (PPIs) that guide enzyme reactivity and timing. While rational design of these PPIs could enable pathway design and modification, this goal remains a challenge due to the complex nature of protein interfaces. Computational methods offer an encouraging avenue, though many score functions fail to predict experimental observables, leading to low success rates. Here, we improve upon the Rosetta score function, leveraging experimental data through iterative rounds of computational prediction and mutagenesis, to design a hybrid fatty acid-non-ribosomal peptide initiation pathway. By increasing the weight of the electrostatic score term, the computational protocol proved to be more predictive, requiring fewer rounds of iteration to identify mutants with high in vitro activity. This allowed efficient design of new PPIs between a non-ribosomal peptide synthetase adenylation domain, PltF, and a fatty acid synthase acyl carrier protein, AcpP, as validated by activity and structural studies. This method provides a promising platform for customized pathway design, establishing a standard for carrier-protein-dependent pathway engineering through PPI optimization.


Assuntos
Proteína de Transporte de Acila , Proteínas de Transporte , Excipientes , Ácido Graxo Sintases , Ácidos Graxos , Redes e Vias Metabólicas
9.
Microbiome ; 11(1): 130, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312139

RESUMO

BACKGROUND: Nudibranchs comprise a group of > 6000 marine soft-bodied mollusk species known to use secondary metabolites (natural products) for chemical defense. The full diversity of these metabolites and whether symbiotic microbes are responsible for their synthesis remains unexplored. Another issue in searching for undiscovered natural products is that computational analysis of genomes of uncultured microbes can result in detection of novel biosynthetic gene clusters; however, their in vivo functionality is not guaranteed which limits further exploration of their pharmaceutical or industrial potential. To overcome these challenges, we used a fluorescent pantetheine probe, which produces a fluorescent CoA-analog employed in biosynthesis of secondary metabolites, to label and capture bacterial symbionts actively producing these compounds in the mantle of the nudibranch Doriopsilla fulva. RESULTS: We recovered the genome of Candidatus Doriopsillibacter californiensis from the Ca. Tethybacterales order, an uncultured lineage of sponge symbionts not found in nudibranchs previously. It forms part of the core skin microbiome of D. fulva and is nearly absent in its internal organs. We showed that crude extracts of D. fulva contained secondary metabolites that were consistent with the presence of a beta-lactone encoded in Ca. D. californiensis genome. Beta-lactones represent an underexplored group of secondary metabolites with pharmaceutical potential that have not been reported in nudibranchs previously. CONCLUSIONS: Altogether, this study shows how probe-based, targeted sorting approaches can capture bacterial symbionts producing secondary metabolites in vivo. Video Abstract.


Assuntos
Produtos Biológicos , Gastrópodes , Animais , Bactérias/genética , Corantes Fluorescentes , Lactonas , Preparações Farmacêuticas
10.
J Med Chem ; 66(10): 6577-6590, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37155693

RESUMO

Highly functionalized skeletons of macrolide natural products gain access to rare spatial arrangements of atoms, where changes in stereochemistry can have a profound impact on the structure and function. Spliceosome modulators present a unique consensus motif, with the majority targeting a key interface within the SF3B spliceosome complex. Our recent preparative-scale synthetic campaign of 17S-FD-895 provided unique access to stereochemical analogues of this complex macrolide. Here, we report on the preparation and systematic activity evaluation of multiple FD-895 analogues. These studies examine the effects of modifications at specific stereocenters within the molecule and highlight future directions for medicinal chemical optimization of spliceosome modulators.


Assuntos
Macrolídeos , Macrolídeos/farmacologia
11.
Methods Mol Biol ; 2670: 49-68, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37184699

RESUMO

Acyl carrier proteins (ACPs) are central to many primary and secondary metabolic pathways. In E. coli fatty acid biosynthesis (FAB), the central ACP, AcpP, transports intermediates to a suite of partner proteins (PP) for iterative modification and elongation. The regulatory protein-protein interactions that occur between AcpP and the PP in FAB are poorly understood due to the dynamic and transient nature of these interactions. Solution-state NMR spectroscopy can reveal information at the atomic level through experiments such as the 2D heteronuclear single quantum coherence (HSQC). The following protocol describes NMR HSQC titration experiments that can elucidate biomolecular recognition events.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Espectroscopia de Ressonância Magnética , Imageamento por Ressonância Magnética
12.
Chem Sci ; 14(15): 4183-4192, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37063797

RESUMO

Herein, we investigate synthetic routes to a close mimic of natural pheomelanin. Three different oxidative polymerization routes were attempted to generate synthetic pheomelanin, each giving rise to structurally dissimilar materials. Among them, the route employing 5-cysteinyl-dihydroxyphenylalanine (5-CD) as a monomer was verified as a close analogue of extracted pheomelanin from humans and birds. The resulting biomimetic and natural pheomelanins were compared via various techniques, including solid-state Nuclear Magnetic Resonance (ssNMR) and Electron Paramagnetic Resonance (EPR). This synthetic pheomelanin closely mimics the structure of natural pheomelanin as determined by parallel characterization of pheomelanin extracted from multiple biological sources. With a good synthetic biomimetic material in hand, we describe cation-π interactions as an important driving force for pheomelanogenesis, further advancing our fundamental understanding of this important biological pigment.

13.
Cell Rep Med ; 4(3): 100962, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36889320

RESUMO

Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations and mis-splicing fuel therapy-resistant leukemia stem cell (LSC) generation in adults, splicing deregulation has not been extensively studied in pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses of FACS-purified hematopoietic stem and progenitor cells followed by differential splicing analyses, dual-fluorescence lentiviral splicing reporter assays, and the potential of a selective splicing modulator, Rebecsinib, in pAML. Using these methods, we discover transcriptomic splicing deregulation typified by differential exon usage. In addition, we discover downregulation of splicing regulator RBFOX2 and CD47 splice isoform upregulation. Importantly, splicing deregulation in pAML induces a therapeutic vulnerability to Rebecsinib in survival, self-renewal, and lentiviral splicing reporter assays. Taken together, the detection and targeting of splicing deregulation represent a potentially clinically tractable strategy for pAML therapy.


Assuntos
Leucemia Mieloide Aguda , Células-Tronco , Adulto , Criança , Humanos , Splicing de RNA/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Isoformas de Proteínas/genética , Mutação , Fatores de Processamento de RNA/genética , Proteínas Repressoras/genética
14.
Cell Stem Cell ; 30(3): 250-263.e6, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36803553

RESUMO

Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation and therapeutic resistance in 20 malignancies. Previously, predicting and preventing ADAR1p150-mediated malignant RNA editing represented a significant challenge. Thus, we developed lentiviral ADAR1 and splicing reporters for non-invasive detection of splicing-mediated ADAR1 adenosine-to-inosine (A-to-I) RNA editing activation; a quantitative ADAR1p150 intracellular flow cytometric assay; a selective small-molecule inhibitor of splicing-mediated ADAR1 activation, Rebecsinib, which inhibits leukemia stem cell (LSC) self-renewal and prolongs humanized LSC mouse model survival at doses that spare normal hematopoietic stem and progenitor cells (HSPCs); and pre-IND studies showing favorable Rebecsinib toxicokinetic and pharmacodynamic (TK/PD) properties. Together, these results lay the foundation for developing Rebecsinib as a clinical ADAR1p150 antagonist aimed at obviating malignant microenvironment-driven LSC generation.


Assuntos
Adenosina Desaminase , Células-Tronco Hematopoéticas , Camundongos , Animais , Isoformas de Proteínas , Adenosina Desaminase/genética
15.
J Med Chem ; 66(4): 2789-2803, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36735827

RESUMO

Human carbonic anhydrase II (hCAII) is a metalloenzyme essential to critical physiological processes in the body. hCA inhibitors are used clinically for the treatment of indications ranging from glaucoma to epilepsy. Targeted protein degraders have emerged as a promising means of inducing the degradation of disease-implicated proteins by using the endogenous quality control mechanisms of a cell. Here, a series of heterobifunctional degrader candidates targeting hCAII were developed from a simple aryl sulfonamide fragment. Degrader candidates were functionalized to produce either cereblon E3 ubiquitin ligase (CRBN) recruiting proteolysis targeting chimeras (PROTACs) or adamantyl-based hydrophobic tags (HyTs). Screens in HEK293 cells identified two PROTAC small-molecule degraders of hCA. Optimization of linker length and composition yielded a degrader with sub-nanomolar potency and sustained depletion of hCAII over prolonged treatments. Mechanistic studies suggest that this optimized degrader depletes hCAII through the same mechanism as previously reported CRBN-recruiting heterobifunctional degraders.


Assuntos
Anidrase Carbônica II , Ubiquitina-Proteína Ligases , Humanos , Proteólise , Anidrase Carbônica II/metabolismo , Células HEK293 , Ubiquitina-Proteína Ligases/metabolismo , Proteínas/metabolismo
16.
Chem Commun (Camb) ; 59(8): 1014-1017, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36645064

RESUMO

Acyl-homoserine lactone synthases make specific AHL quorum sensing signals to aid virulence in Gram-negative bacteria. Here, we use solution NMR spectroscopy to demonstrate that the carrier protein-enzyme interface accurately reveals substrate recognition mechanisms in two quorum signal synthases.


Assuntos
Proteínas de Bactérias , Proteínas de Transporte , Proteínas de Transporte/metabolismo , Proteínas de Bactérias/metabolismo , Bactérias Gram-Negativas/metabolismo , Percepção de Quorum , Virulência , Acil-Butirolactonas/química , Acil-Butirolactonas/metabolismo
17.
Acta Crystallogr D Struct Biol ; 78(Pt 9): 1171-1179, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048156

RESUMO

Ketosynthases (KSs) catalyse essential carbon-carbon bond-forming reactions in fatty-acid biosynthesis using a two-step, ping-pong reaction mechanism. In Escherichia coli, there are two homodimeric elongating KSs, FabB and FabF, which possess overlapping substrate selectivity. However, FabB is essential for the biosynthesis of the unsaturated fatty acids (UFAs) required for cell survival in the absence of exogenous UFAs. Additionally, FabB has reduced activity towards substrates longer than 12 C atoms, whereas FabF efficiently catalyses the elongation of saturated C14 and unsaturated C16:1 acyl-acyl carrier protein (ACP) complexes. In this study, two cross-linked crystal structures of FabB in complex with ACPs functionalized with long-chain fatty-acid cross-linking probes that approximate catalytic steps were solved. Both homodimeric structures possess asymmetric substrate-binding pockets suggestive of cooperative relationships between the two FabB monomers when engaged with C14 and C16 acyl chains. In addition, these structures capture an unusual rotamer of the active-site gating residue, Phe392, which is potentially representative of the catalytic state prior to substrate release. These structures demonstrate the utility of mechanism-based cross-linking methods to capture and elucidate conformational transitions accompanying KS-mediated catalysis at near-atomic resolution.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Proteínas de Escherichia coli , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Carbono/metabolismo , Catálise , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Ácido Graxo Sintase Tipo II , Ácidos Graxos Insaturados/metabolismo
18.
ACS Chem Biol ; 17(10): 2890-2898, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36173802

RESUMO

Non-ribosomal peptides play a critical role in the clinic as therapeutic agents. To access more chemically diverse therapeutics, non-ribosomal peptide synthetases (NRPSs) have been targeted for engineering through combinatorial biosynthesis; however, this has been met with limited success in part due to the lack of proper protein-protein interactions between non-cognate proteins. Herein, we report our use of chemical biology to enable X-ray crystallography, molecular dynamics (MD) simulations, and biochemical studies to elucidate binding specificities between peptidyl carrier proteins (PCPs) and adenylation (A) domains. Specifically, we determined X-ray crystal structures of a type II PCP crosslinked to its cognate A domain, PigG and PigI, and of PigG crosslinked to a non-cognate PigI homologue, PltF. The crosslinked PCP-A domain structures possess large protein-protein interfaces that predominantly feature hydrophobic interactions, with specific electrostatic interactions that orient the substrate for active site delivery. MD simulations of the PCP-A domain complexes and unbound PCP structures provide a dynamical evaluation of the transient interactions formed at PCP-A domain interfaces, which confirm the previously hypothesized role of a PCP loop as a crucial recognition element. Finally, we demonstrate that the interfacial interactions at the PCP loop 1 region can be modified to control PCP binding specificity through gain-of-function mutations. This work suggests that loop conformational preferences and dynamism account for improved shape complementary in the PCP-A domain interactions. Ultimately, these studies show how crystallographic, biochemical, and computational methods can be used to rationally re-engineer NRPSs for non-cognate interactions.


Assuntos
Peptídeo Sintases , Peptídeos , Sequência de Aminoácidos , Peptídeo Sintases/metabolismo , Peptídeos/química , Domínio Catalítico , Proteínas de Transporte/metabolismo
19.
Sci Total Environ ; 850: 158761, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36154974

RESUMO

Accumulation of plastics in the Earth's oceans is causing widespread disruption to marine ecosystems. To help mitigate the environmental burden caused by non-degradable plastics, we have previously developed a commercially relevant polyurethane (PU) foam derived from renewable biological materials that can be depolymerized into its constituent monomers and consumed by microorganisms in soil or compost. Here we demonstrate that these same PU foams can be biodegraded by marine microorganisms in the ocean and by isolated marine microorganisms in an ex situ seawater environment. Using Fourier-transform infrared (FTIR) spectroscopy, we tracked molecular changes imparted by microbial breakdown of the PU polymers; and utilized scanning electron microscopy (SEM) to demonstrate the loss of physical structure associated with colonization of microorganisms on the PU foams. We subsequently enriched, isolated, and identified individual microorganisms, from six marine sites around San Diego, CA, that are capable of depolymerizing, metabolizing, and accumulating biomass using these PU foams as a sole carbon source. Analysis using SEM, FTIR, and gas chromatography-mass spectrometry (GCMS) confirmed that these microorganisms depolymerized the PU into its constitutive diols, diacids, and other PU fragments. SEM and FTIR results from isolated organismal biodegradation experiments exactly matched those from ex situ and ocean biodegradation samples, suggesting that these PU foam would undergo biodegradation in a natural ocean environment by enzymatic depolymerization of the PU foams and eventual uptake of the degradation products into biomass by marine microorganisms, should these foams unintentionally end up in the marine environment, as many plastics do.


Assuntos
Ecossistema , Poliuretanos , Biodegradação Ambiental , Carbono , Plásticos , Poliuretanos/química , Solo
20.
Molecules ; 27(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35956835

RESUMO

To realize the commercialization of sustainable materials, new polymers must be generated and systematically evaluated for material characteristics and end-of-life treatment. Polyester polyols made from renewable monomers have found limited adoption in thermoplastic polyurethane (TPU) applications, and their broad adoption in manufacturing may be possible with a more detailed understanding of their structure and properties. To this end, we prepared a series of bio-based crystalline and amorphous polyester polyols utilizing azelaic acid and varying branched or non-branched diols. The prepared polyols showed viscosities in the range of 504-781 cP at 70 °C, with resulting TPUs that displayed excellent thermal and mechanical properties. TPUs prepared from crystalline azelate polyester polyol exhibited excellent mechanical properties compared to TPUs prepared from amorphous polyols. These were used to demonstrate prototype products, such as watch bands and cup-shaped forms. Importantly, the prepared TPUs had up to 85% bio-carbon content. Studies such as these will be important for the development of renewable materials that display mechanical properties suitable for commercially viable, sustainable products.


Assuntos
Ácidos Dicarboxílicos , Poliuretanos , Álcoois , Poliésteres , Poliuretanos/química
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