Formation Of Ester Bonds Research Articles

Interfacial adhesion of a grafted polymer on a cellulose surface: a first-principles study

This paper presents the first-principles investigation on interfacial adhesive strength between grafted polymer and cellulose. Focusing on maleic anhydride-grafted polypropylene, which is expected to be used in various applications including automobiles, a simple interfacial model was constructed under a local tensile loading condition. Then the stress–strain relation, deformation of molecular structure and breaking process were discussed. From comparison of mechanical responses among three chemically possible bonding configurations, it was clarified that the monoester bond exhibited higher interfacial strength than the diester bond. We also found that controlling the bonding configuration can improve the interface strength by about 50% compared to when primary OH groups react to form ester bonds. It was proved that this first-principles calculation model was effective for the definitive design and development of chemical modification of nanocellulose.

Structural and dimensional analysis of LDPE/TPS blend filled with calcium carbonate

This study aims to investigates the changes in structural, thermal stability and water absorption properties of thermoplastic starch (TPS) before and after modification with citric acid and ascorbic acid. The first stage of study involved the preparation of TPS from native potato starch. Starch will be converted into thermoplastic like in the presence of glycerol as plasticizer. For the second stage, LDPE was blended with TPS to produce LDPE/TPS blend with and without modification. Then, the influence of calcium carbonate as particulate filler on the properties of LDPE/TPS blends was also investigated. Structural findings based on the FTIR analysis showed the formation of new ester bond on the TPS backbone after the modification, which correspond to the formation of crosslinking network in TPS phase. Water absorption test was used to determine the effectiveness of TPS modification in term of physical interaction between the phases.

Magnetic bead-based electrochemical and colorimetric assays of circulating tumor cells with boronic acid derivatives as the recognition elements and signal probes

Simple, sensitive and rapid detection of circulating tumor cells (CTCs) is of great importance for early diagnosis and therapy of cancers. Overexpression of sugar units on cell surface is related to the phenotypes of many cancers. Based on the boronate ester interaction, we reported the electrochemical and colorimetric detection of CTCs with high simplicity and sensitivity. Specifically, ferroceneboronic acid (FcBA) can be measured by differential pulse voltammetry and 4-mercaptophenylboronic acid (MPBA) can induce the aggregation and color change of gold nanoparticles (AuNPs). CTCs captured by the aptamer-modified magnetic beads (Apt-MBs) can sequestrate FcBA or MPBA molecules by the formation of boronate ester bonds, thus leading to the decrease in the electrochemical signal of FcBA or preventing the MPBA-triggered aggregation of AuNPs. Due to the overexpression of sugar groups on the surface of CTCs, the amplification-free methods exhibited high sensitivity and obviated the use of additional antibody or aptamer for the recognition of captured cells. With MCF-7 cancer cell as the model, 50 cells can be readily determined by the electrochemical and colorimetric methods. The proposed strategy is valuable for probing of cell glycosylation and designing of novel sensing devices for detection of sugar-containing biological macromolecules and cells.

Partial purification and biochemical characterization of an alkaline esterase from Sorghum bicolor

Esterases are enzymes that present good potential for industrial applications since they catalyze the formation or cleavage of ester bonds in water-soluble substrates, and sorghum seeds can represent an alternative source of this enzyme. The extraction of esterase from sorghum seeds is an economical alternative to obtain an enzyme of great interest. Esterases may improve the quality or accelerate the maturation of cheeses, cured bacon and fermented sausages and may also resolve racemic mixtures. Recently, seed esterases have been the focus of much attention as biocatalysts. In some cases, these enzymes present advantages over animal and microbial lipases due to some quite interesting features such as specificity and low cost, being a great alternative for their commercial exploitation as industrial enzymes The esterase studied here was extracted from sorghum seeds and some of its biochemical properties determined using synthetic substrates (p-nitrophenyl butyrate, caprylate, laurate and palmitate). The enzyme presented optimum activity at pH 8.0 and was stable in all the pH ranges studied. The optimum temperature for its activity was 40ºC but it showed low stability at this temperature (40% relative activity). The values derived for Km and Vmax were 0.67mM and 125 U.mg-1, respectively, obtained using p-nitrophenyl butyrate as the substrate. The enzyme showed an increase in activity when K2HPO4 was added to the reaction medium, but the ions Mn2+, CO+, Hg+ and Fe2+ strongly inhibited the enzyme activity. This enzyme showed a preference for the hydrolysis of short chain fatty acids. The characteristics of sorghum esterase are very similar to those of the microbial esterases used in detergent processing.

Adsorption and Release of Rose Bengal on Layer-by-Layer Films of Poly(Vinyl Alcohol) and Poly(Amidoamine) Dendrimers Bearing 4-Carboxyphenylboronic Acid

Phenylboronic acid-bearing polyamidoamine dendrimer (PBA-PAMAM)/poly(vinyl alcohol) (PVA) multilayer films were prepared through the layer-by-layer (LbL) deposition of PBA-PAMAM solution and PVA solution. PBA-PAMAM/PVA films were constructed successfully through the formation of boronate ester bonds between the boronic acid moiety in PBA and 1,3-diol units in PVA. When the (PBA-PAMAM/PVA)5 films were immersed in rose bengal (RB) solution, RB was adsorbed onto the LbL films. The amount of RB adsorbed was higher in the LbL films immersed in acidic solution than in basic solution. The release of RB from the LbL films was also promoted in the basic solution, while it was suppressed in the acidic solution. The boronic acid ester is oxidized to phenol by hydrogen peroxide (H2O2) and the carbon-boron bond is cleaved, so that the (PBA-PAMAM/PVA)5 films can be decomposed by immersion in H2O2 solution. Therefore, when RB-adsorbed (PBA-PAMAM/PVA)5 films were immersed in H2O2 solution, the release of RB was moderately promoted when the solution was weakly acidic.

Development and Evaluation of Thermally-Crosslinked Mucoadhesive Gantrez<sup>TM </sup>S-97/Polyvinyl Alcohol/ Hyaluronic Acid-Catechol Nanofibers

This study aimed to develop novel thermally crosslinked mucoadhesive nanofibers. The nanofiber patches were composed of mucoadhesive polymers which were catechol-bearing hyaluronic acid (HA-cat) and copolymer of methyl vinyl ether and maleic anhydride (GantrezTM, GT). Polyvinyl alcohol was used to improve the nanofiber properties. The nanofibers were prepared from a polymer mixture of 20 %wt GT, 10 %wt PVA, and 2 %wt HA-cat at different ratios using an electrospinning technique. Crosslinking process was performed by heat treatment at 130 °C for various durations. The appearances and chemical characteristics of the patch was evaluated using scanning electron microscope (SEM) and attenuated total reflectance Fourier-transformed infrared spectroscopy (ATR-FTIR), respectively. Moreover, the percentage of water insolubilization, tensile strength, and mucoadhesive property of the electrospun nanofibers were evaluated. Different polymer ratios provided identical nanoscale fibers. The patch prepared at the GT:PVA:HA-cat ration of 1:1:2 which provided the highest amount of catechol was selected. The optimal crosslinking time was 2 h under 130 °C in which the fiber diameters were not altered, and the highest percentage of water insolubilization was observed. Hydrogen and ester bond formation were established from the ATR-FTIR spectrum of the crosslinked patch. The patch could resist the force applied up to 4.82±0.46 N prior to deformation. In addition, the maximum detachment force from porcine buccal mucosa was 0.08±0.01 N. After all, the prepared electrospun mucoadhesive nanofibers may be a favorable mucoadhesive material for transmucosal drug delivery.

Pineapple Peel Extract as an Effective Substrate for Esterase Production from Bacillus subtilis E9.

Esterase, belonging to hydrolase class of enzymes catalyzes the cleavage and formation of ester bonds. Esterase producing isolates E9 and E46, isolated from pineapple waste enriched soil were identified as Bacillus subtilis E9 and Bacillus sp. E46 respectively. Bacillus subtilis E9 with 10 U/mg esterase activity in basal media was further chosen for media optimization studies. Several factors including the effect of organic solvents and fruit peel extracts were studied by one factor at a time optimization method and statistical models. An enhanced enzyme production of 250.50U/mg could be obtained under the optimal conditions of pH 6.5, incubation time 25h and 1.8%v/v of acetone extract of pineapple peel. The four-stage purification improved the purity of the enzyme by 1.5-fold with 5.3% recovery and specific activity of 384U/mg. The monomeric nature and the molecular weight (45 KDa) of the enzyme were determined by performing SDS PAGE and its activity was confirmed by zymogram analysis. The substrate specificity of the purified fraction exhibited a higher activity towards lower chain length esters, indicating the enzyme as esterase. The partially purified esterase showed an optimal temperature of 40°C at an optimum pH of 7. Km and Vmax of the enzyme were 1.12mM and 1.18mM of released pNP · min-1 respectively.

<i>Myristica fragrans</i> Shells as Potential Low Cost Bio-Adsorbent for the Efficient Removal of Rose Bengal from Aqueous Solution: Characteristic and Kinetic Study

In the present study, the Myristica fragrans shells (MFS) was used as low-cost bio adsorbent for the removal of Rose Bengal (RB) dye from aqueous solutions. The characteristics of MFS powder were studied before and after adsorption using different techniques such as Fourier transform Infrared spectroscopy (FTIR), Thermal Gravimetric Analysis (TGA), BET and BJH surface area analysis, Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Batch adsorption was adopted to evaluate the effect of various parameters on the removal of RB such as; time of contact (5–75 min), initial dye concentration (10–50 mg L–1), adsorbent dose (0.1–1.7 g L–1) and pH (3–12). The results revealed that the coverage of MFS surface by RB molecules involved the formation of ester bond (esterification), and the pore diameter decreased from 190.55 to 2.43 nm when adsorption of RB onto MFS surface occurred. Experimental adsorption data were modelled using isotherm models including Langmuir, Freundlich, and Temkin. Temkin isotherm demonstrated to be the best isothermal model, and the results indicate that the adsorption of Rose Bengal on MFS surface follows pseudo second-order kinetics model. The adsorption of dye at different pH media showed that the esterification process was more preferred in acidic solution.

Polyhydroxybutyrate Bioresins with High Thermal Stability by Cross-linking with Resorcinol Diglycidyl Ether.

The development of sustainable materials by employing natural and nontoxic resources has been attracting much attention over the previous years. In this work, we discuss for the first time the chemical combination between resorcinol diglycidyl ether (RDGE), an aromatic biobased thermosetting monomer, and polyhydroxybutyrate (PHB), a bioderived and biodegradable thermoplastic polyester. By this combination, we aimed to associate the high thermal stability of RDGE with a toughening effect by the aliphatic chains of PHB. The investigations on the mechanism of the cross-linking reaction and on the structural connectivity between the two components were realized by Fourier transform infrared (FTIR) and NMR spectroscopies. We found that the epoxide polymerization catalyzed by tertiary amines triggers the formation of crotonyl species by polyhydroxybutyrate cleavage. Two-dimensional NMR experiments show that polyhydroxybutyrate fragments covalently bind as side chains to the rigid aromatic network of the epoxide frame. The cross-linking between the two systems entails the formation of new ester and ether bonds. The obtained structures show a network homogeneity confirmed by a single Tg, from 85 to 47 °C, as a function of the formulation, and tan δ values from 87 to 53 °C. The combination of the two comonomers showed a positive effect. The PHB increased the toughness of RDGE-based thermosets, improving the material elasticity by increasing the chain length between the cross-links. An important result of this study is the high thermal stability of RDGE/PHB bioresins, with the T5% varying between 330 and 310 °C as a function of the PHB ratio.

Synthesis and Characterization of Zinc Phthalocyanine-Cellulose Nanocrystal (CNC) Conjugates: Toward Highly Functional CNCs.

We report highly fluorescent cellulose nanocrystals (CNCs) formed by conjugating a carboxylated zinc phthalocyanine (ZnPc) to two different types of CNCs. The conjugated nanocrystals (henceforth called ZnPc@CNCs) were bright green in color and exhibited absorption and emission maxima at ∼690 and ∼715 nm, respectively. The esterification protocol employed to covalently bind carboxylated ZnPc to surface hydroxyl group rich CNCs was expected to result in a monolayer of ZnPc on the surface of the CNCs. However, dynamic light scattering (DLS) studies indicated a large increase in the hydrodynamic radius of CNCs following conjugation to ZnPc, which suggests the binding of multiple ZnPc molecular layers on the CNC surface. This binding could be through co-facial π-stacking of ZnPc, where ZnPc metallophthalocyanine rings are horizontal to the CNC surface. The other possible binding mode would give rise to conjugated systems where ZnPc metallophthalocyanine rings are oriented vertically on the CNC surface. Density functional theory based calculations showed stable geometry following the conjugation protocol that involved covalently attached ester bond formation. The conjugates demonstrated superior performance for potential sensing applications through higher photoluminescence quenching capabilities compared to pristine ZnPc.

Responsive boron biomaterials and their biomedical applications

Due to the formation of dynamic boronate ester bonds between phenylboronic acid (PBA) and 1,2- and 1,3-diols, PBA-containing biomaterials show increasing applications in biomedical areas, including responsive nanobiomaterials for targeting delivery of chemical drugs, protein drugs, gene drugs and imaging agents in vitro and in vivo for detection of various bioactive molecules such as sialic acid, saccharides, adenosine triphosphate (ATP) and dopamine. With the specific reaction between PBA and sialic acid, which is overexpressed in many kinds of cancer cells, PBA has been used as a targeting moiety for tumor-targeting drug delivery. Additionally, PBA as an electron acceptor affords nanomaterials Lewis acid-base coordination with electron donor atoms such as nitrogen and oxygen, which can be exploited for developing drug delivery systems with high drug loading. Furthermore, PBA-containing materials can stoichiometric consume reactive oxygen species (ROS) and show a nucleus targeting ability. This current review outlined PBA-containing biomaterials with various responsive abilities including sialic acid-targeting, sugars-binding, ROS-response, ATP-response, dopamine-binding, and nuclear targeting. On this basis, their biomedical applications were summarized.

Gas-Phase Dissociation Chemistry of Deprotonated RGD.

We investigate the structure and dissociation pathways of the deprotonated amphoteric peptide arginylglycylasparic acid, [RGD-H]-. We model the pertinent gas-phase structures and fragmentation chemistry of the precursor anions and predominant sequence-informative bond cleavages (b2+H2O, c2, and z1 peaks) and compare these predictions to our tandem mass spectra and infrared spectroscopy experiments. Formation of the b2+H2O anions requires rate-limiting intramolecular back biting to cleave the second amide bond and generate an anhydride structure. Facile cleavage of the newly formed ester bond with concerted expulsion of a cyclic anhydride neutral generates the product structure. IR spectroscopy supports this b2+H2O anion having structures that are essentially identical to C-terminally deprotonated arginylglycine, [RG-H]-. Formation of the c2 anion is predicted to require concerted expulsion of CO2 from the aspartyl side chain carboxylate and cleavage of the N-Calpha bond to produce a proton-bound dimer of arginylglycinamide and acrylate. Proton transfers within the dimer then enable predominant detection of a c2 anion with the negative charge nominally on the central, glycine nitrogen (amidate structure) as the proton affinity of this structure is predicted to be lower than acrylate by ∼27 kJ mol-1. Alternate means of cleaving the same N-Calpha bond produce deprotonated cis-1,4-dibut-2-enoic acid z1 anion structures. These lowest energy processes involve C-H proton mobilization from the aspartyl side chain prior to N-Calpha bond cleavage consistent with proposals from the literature.

Structural characterization of the lignin from Saxifraga (Saxifraga oppositifolia L.) stems

As a renewable source of unique aromatic compounds, lignin attracts the attention of many researchers. However, for its successful application, it is necessary to have a clear and accurate idea of its chemical structure. Therefore, it is necessary to expand knowledge about the structure of lignins of various nature using the informative analytical methods. The aim of this study was to characterize the dioxane lignin of the Saxifraga oppositifolia L. — the northernmost angiosperm. The lignin of plants growing in the Arctic zone may differ significantly from other plants, both due to species differences and peculiarities of growing conditions. Studies were conducted on an isolated lignin preparation obtained by the Pepper's method. Analysis of Py-GC/MS data and NMR spectroscopy showed that saxifrage lignin belongs to GH-type. This is evidenced by a significant proportion of p-hydroxyphenyl units (40%), while the content of syringyl units is about 14%. The major substructures of the studied lignin were β-aryl ether, phenylcoumaran, and resinol. It was found that the γ‑carbon of the lignin side chains are partly acetylated, and forms ester bonds with the p-hydroxybenzoate structure. In addition, the NMR spectrum showed a signal of the phenylglycoside evidenced the presence of the lignin-carbohydrate complex.

Modification of Alkyd with Epoxy and its Application for Paint Part 1: Epoxy Alkyd Ester Manufacturing and some Properties of Paint made from this Ester

The article introduces the modification of alkyd resin by epoxy resin to make epoxy alkyd ester. The study investigated the effects of reflux xylene content, the proportion of the constituents participating in the esterification reaction on the reaction processing and acidity index of the product. The infrared (IR) spectroscopy results confirmed the formation of ester bonds after the reaction. The paper also studied the mechanical properties of paint film based on the synthesized ester epoxy alkyd and compared them with the alkyd paint, the results showed that impact resistance and hardness of the study sample were higher than those of the alkyd paint sample. In addition, investigation, comparison of thermal stability of alkyd paint and epoxy alkyd paint film were also mentioned.
 Keywords: Epoxy alkyd esters, mechanical properties, thermal endurance, drying time.

Genetic evidences for the core biosynthesis pathway, regulation, transport and secretion of liamocins in yeast-like fungal cells.

So far, it has been still unknown how liamocins are biosynthesized, regulated, transported and secreted. In this study, a highly reducing polyketide synthase (HR-PKS), a mannitol-1-phosphate dehydrogenase (MPDH), a mannitol dehydrogenase (MtDH), an arabitol dehydrogenase (ArDH) and an esterase (Est1) were found to be closely related to core biosynthesis of extracellular liamocins in Aureobasidium melanogenum 6-1-2. The HR-PKS was responsible for biosynthesis of 3,5-dihydroxydecanoic acid. The MPDH and MtDH were implicated in mannitol biosynthesis and the ArDH was involved in arabitol biosynthesis. The Est1 catalyzed ester bond formation of them. A phosphopantetheine transferase (PPTase) activated the HR-PKS and a transcriptional activator Ga11 activated expression of the PKS1 gene. Therefore, deletion of the PKS1 gene, all the three genes encoding MPDH, MtDH and ArDH, the EST1, the gene responsible for PPTase and the gene for Ga11 made all the disruptants (Δpks13, Δpta13, Δest1, Δp12 and Δg11) totally lose the ability to produce any liamocins. A GLTP gene encoding a glycolipid transporter and a MDR1 gene encoding an ABC transporter took part in transport and secretion of the produced liamocins into medium. Removal of the GLTP gene and the MDR1 gene resulted in a Δgltp1 mutant and a Δmdr16 mutant, respectively, that lost the partial ability to secrete liamocins, but which cells were swollen and intracellular lipid accumulation was greatly enhanced. Hydrolysis of liamocins released 3,5-dihydroxydecanoic acid, mannitol, arabitol and acetic acid. We proposed a core biosynthesis pathway, regulation, transport and secretion of liamocins in A. melanogenum.

Old corrugated box (OCB)-based cellulose nanofiber-reinforced and citric acid-cross-linked TSP–guar gum composite film

Old corrugated box (OCB) as a raw material was treated using alkali, acetic acid with NaClO and hydrogen peroxide to extract partially purified cellulose microfibers. FTIR and XRD analysis indicates the significant removal of non-cellulosic (lignin and hemicelluloses) content, followed by a notable increase in cellulose purity and crystallinity. Obtained cellulose microfibers (diameter 60–70 µm) were broken down to cellulose nanofibers (diameter up to 80 nm) using high-pressure homogenizer at 1700–1800 bar pressure consisting of 30 cycles and further characterized by SEM and XRD. Later on, nanocomposite films were prepared and optimized for required citric acid concentration for cross-linking with tamarind seed polysaccharide/guar gum blend by polycondensation reaction. And plasticized by glycerol (0.5% w/v) with different concentrations of OCB-CNF (0.1–1% w/v). The cross-link reaction was optimized at 80 °C for 3 h in order to confirm the esterification reaction between citric acid, polysaccharide and nanofiber. Increasing characteristic band intensity at around 1731 cm−1 represents ester bond formation is supported by the FTIR analysis. Rheology reveals the increase in cross-linking density after citric acid cross-link at 0.2% of OCB-CNF. Improvement in interfacial bonding between nanofiber and matrix results in enhanced tensile strength, barrier property and thermal stability as compared to those of control film. In addition, swelling behavior of OCB-CNF composite films was studied at different pH conditions (pH = 3, 7 and 10), where 0.2% and 0.5% OCB-CNFs showed better interaction with the matrix polysaccharide.

Investigation of polymers and alcohols produced in oxidized soybean oil at frying temperatures

Although significant amounts of polymers associated with adverse health effects in oils are produced during frying, the chemical bonds forming these polymers are not well understood. This study revealed that ester bonds are responsible for the polymerization of soybean oil during frying and heating at 175 °C. The ester value of soybean oil increased during frying up to day 3 of the experiment and slightly decreased on day 4 of the experiment indicating that esterification and hydrolysis concomitantly occurred. The 13C NMR spectra showed further evidence of the formation of ester bonds. This study also examined unidentified chemical bonds in the polymer products, other than ester bonds, with NMR spectroscopy. No NMR signals indicating ether bonds were observed. The NMR study after the reaction of oxidized soybean oil with acetyl chloride clarified assignments of proton signals, confirming some previous assignments, and assigning a new proton signal as an alcohol.

Structural Determination of a New Peptidolipid Family from Rhodococcus opacus and the Pathogen Rhodococcus equi by Multiple Stage Mass Spectrometry.

The cell walls of the genus Rhodococcus including the pathogenic bacterium Rhodococcus equi (R. equi) and biotechnologically important bacterium Rhodococcus opacus (R. opacus) contain an abundant peptidolipid (or termed lipopeptide) family whose structures have not been reported previously. Here, we describe a linear ion-trap multiple-stage mass spectrometric (LIT MSn) approach with high resolution mass spectrometry (HRMS), in conjunction with NMR spectroscopy, chemical reactions, and GC/MS analysis to define the structures of these compounds. We employed LIT MSn (n = 2-8) on the [M + Na]+ ion species to establish the peptide sequence, the identity of the fatty acyl substituent, and its location within the molecule, while NMR spectroscopy and GC/MS were used to recognize the Leu and Ile moieties. The major new lipopeptide found in R. opacus is defined as C17H35CH(OH)CH2CO-NHLeu-Ser-Leu-Ile-Thr-Ile-PheCOOH, where a β-OH fatty acyl (C18-C22) substituent is attached to the N-terminal of the LSLITIF peptide chain via a NH-CO bond. By contrast, the main peptidolipids found in R. equi belong to the cyclopeptidolipid family, which possesses the same peptide sequence and lipid chain, but the β-OH group of the fatty acyl moiety and the C-terminus of the peptide (i.e., the -COOH) are cyclized by an ester bond formation to a lactone, with a structure similar to iturin-A (Peypoux, F. et al. Biochemistry 1978, 17, 3992-3996). The antibiotic activity test of these new lipids did not reveal an activity against any of seven microorganisms tested.

Tumor- and mitochondria-targeted nanoparticles eradicate drug resistant lung cancer through mitochondrial pathway of apoptosis

Chemotherapeutic drugs frequently encounter multidrug resistance. ATP from mitochondria helps overexpression of drug efflux pumps to induce multidrug resistance, so mitochondrial delivery as a means of “repurposing’’ chemotherapeutic drugs currently used in the clinic appears to be a worthwhile strategy to pursue for the development of new anti-drug-resistant cancer agents. TPP-Pluronic F127-hyaluronic acid (HA) (TPH), with a mitochondria-targeting triphenylphosphine (TPP) head group, was first synthesized through ester bond formation. Paclitaxel (PTX)-loaded TPH (TPH/PTX) nanomicelles exhibited excellent physical properties and significantly inhibited A549/ADR cells. After TPH/PTX nanomicelles entered acidic lysosomes through macropinocytosis, the positively charged TP/PTX nanomicelles that resulted from degradation of HA by hyaluronidase (HAase) in acidic lysosomes were exposed and completed lysosomal escape at 12 h, finally localizing to mitochondria over a period of 24 h in A549/ADR cells. Subsequently, TPH/PTX caused mitochondrial outer membrane permeabilization (MOMP) by inhibiting antiapoptotic Bcl-2, leading to cytochrome C release and activation of caspase-3 and caspase-9. In an A549/ADR xenograft tumor model and a drug-resistant breast cancer-bearing mouse model with lung metastasis, TPH/PTX nanomicelles exhibited obvious tumor targeting and significant antitumor efficacy. This work presents the potential of a single, nontoxic nanoparticle (NP) platform for mitochondria-targeted delivery of therapeutics for diverse drug-resistant cancers.

Heterologous and Engineered Biosynthesis of Nematocidal Polyketide-Nonribosomal Peptide Hybrid Macrolactone from Extreme Thermophilic Fungi.

Fungal polyketide-nonribosomal peptide (PK-NRP) hybrid macrolactones are a growing family of natural products with biomedical and agricultural activities. One of the most important families is the thermolides, which are produced by extreme thermophilic fungi and exhibit strong nematocidal activity. We show here that the genes ThmABCE from Talaromyces thermophilus NRRL 2155 are critical for thermolide synthesis. Two separate single-module hrPKS (ThmA) and NRPS (ThmB) enzymes collaborate to synthesize the core macrolactone backbone (6 or 7), and the NRPS ThmB-CT domain catalyzes the key macrocyclization step in PK-NRP intermediate release via ester bond formation, representing a novel function of fungal NRPS C domains. We also show that heterologous and engineered expression of the Thm genes in the type strains of Aspergillus nidulans and Escherichia coli not only dramatically enhances the yields of thermolides but also affords different esterified analogues, such as butyryl- (thermolides J and K, 15 and 16), hexanoyl-, and octanyl- derivatives or mixed thermolides. Thermolides L and M (18 and 19), discovered via genome mining-based combinatorial biosynthesis, represent the first l-phenylalanine-based thermolides. Our work shows a unique biosynthetic mechanism of PK-NRP hybrid macrolactones from extremophiles, which led to the discovery of novel compounds and furthers our biosynthetic knowledge.