Methods in Enzymology
·
2019
·
IF 1.862
Wan Zhang,Linjun Zhou,Chunyu Li,Zixin Deng,Xudong Qu
Polyketides have valuable pharmaceutical properties and exhibit a high degree of structural diversity. This diversity can trace back to the polyketide synthesis assembly line, in which the gatekeeper domain ATs strictly control the selection and incorporation of the simple extender units. And thus engineering attempts targeted on ATs have been made to obtain novel polyketide skeletons, which are useful for pharmaceutical and cellular function studies. So far, method of combinatorial biosynthesis has become the most attractive and effective way, particularly through alteration of the acyltransferase (AT) specificity. Herein, upon the complex structures of a broadly selective SpnD-AT, we introduce a structure-directed protocol to manipulate the well-studied EryAT6 to broaden its substrate scope. This protocol can also be generalized to canonical AT domains engineering in the generation of novel and useful chemical probes for dissecting cellular functions.
研究领域:
生物化学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2020
·
IF 2.014
Yong-Jiang WANG,Li WANG,Xin HE,Dong-Dong XU,Jun TANG,Ya-Tuan MA,Yi-Jun YAN,Yu-Cheng GU,Jing YANG,Sheng-Xiong HUANG
Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B ( 1 ) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the 15 N -labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.
研究领域:
微生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2020
·
IF 3.862
Shaobai Wang,Kangzhou Xie,Donglin Tang
Polyvinyl alcohol (PVA) is a reactive polymer since there are abundant hydroxyl groups so various chemical transitions are feasible for PVA. In this study, we utilized the oxidation of PVA followed with a ketalization to achieve the configuration of reversible polyketal networks. The oxidation of PVA was performed by using a benign oxidation system in which hydrogen peroxide acts as the green oxidant and p -toluene sulfonic acid (TSA) as the catalyst. Both fully oxidized PVA (polyketone, PK) and partially oxidized PVA (PVA-OXI) were obtained by controlling the oxidation time. Polyketals (PKLs) were prepared by ketalization of PVA with PK, or by self-ketalization of PVA-OXI. Under the catalysis TSA , only dark PKLs were obtained. However, with ionic liquid [BMIm]HSO 4 as the catalyst, PKLs were colorless and transparent. The PKLs originated from a feed ratio of PVA/PK = 4/1 (w/w) seems tougher than other samples. When the PKL films were hydrolysed at 90 °C and recasted, the recycled (or reprocessed) PKL films appears the same as the fresh one, from the appearance to the chemical structure, and further to the mechanical properties. PKLs can be prepared by self-ketalization as well from PVA-OXI but the mechanical properties of the obtained PKLs seem not as good as those from ketalization of PVA and PK. The discoveries in this work open a door to easy but efficient modification of OH-abundant polymers, especially for polysaccharides.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
AUSTRALIAN JOURNAL OF CHEMISTRY
·
2018
·Vol. 71
·期 6
·449-454
·
IF 1.059
Fu-Rong Zeng,Qi-Lin Zhu,Zi-Long Li
Post-polymerization modification is a facile and efficient method for the generation of diverse functional polymers. Herein, polymer-based molecular arrays were obtained by using sequential modification. First, periodic polyketone P0 was synthesized via acyclic diene metathesis (ADMET) polymerization of α,ω-diene M0. Oxime chemistry was employed in the functionalization of the ketone moieties of P0 using three commercially available alkoxyamine hydrochlorides. Finally, electrophilic alkoxyetherification, a four-component reaction, was employed in the modification of alkene groups on polymer main chains using N-bromosuccinimide (NBS), tetrahydrofuran, and fluorinated carboxylic acid. Complete conversion of reactive sites was observed in both steps, and the two modification reactions exhibited excellent compatibility. The thermal properties of the polymers as thermal stability, and glass transition and melting behaviours were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC).
研究领域:
材料科学
·
有机化学
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Yu-Qi Gao,Shuang-Tian Du,Jian Xiao,Da-Cheng Wang,Wen-Bo Han,Qiang Zhang,Jin-Ming Gao
Two biosynthetically related new metabolites, eucalyptacid A (1) and eucalactam B (2), along with six known compounds (3–8), eugenitol (3), cytosporone C (4), 4-hydroxyphenethyl alcohol (5), 1-(4-hydroxyphenyl)ethane-1,2-diol (6), N-(2-hydroxy-2-phenylethyl)acetamide (7), and phomopene (8), were isolated from the solid rice cultures of the endophytic fungus Diaporthe eucalyptorum KY-9 that had been isolated from Melia azedarach. Also, two further new derivatives (2a, 2b) were prepared from 2. The structures were elucidated by exhaustive analysis of NMR and ESIMS data and chemical methods such as Marfey’s protocol. Compound 1 was identified as a rare polyketide fatty acid, (8E)-3,5,11-trihydroxy-2,10,12-trimethyltetradecenoic acid, and 2 was determined to be the first cyclic depsipeptide containing the same fatty acid unit as 1 and a Gly-Gly-Thr tripeptide chain. Its N-terminal end is N-acylated by an 11-hydroxy fatty acid with a branch alkyl chain of 14:1. The 11-hydroxyl group connects to the carboxylic group of the C-terminal amino acid to form a 22-membered lactone ring. A hypothetical biosynthetic pathway for the new polyketides is proposed. The isolated compounds were assayed for their inhibition against four plant pathogenic fungi, Alternaria solani, Botrytis cinerea, Fusarium solani, and Gibberella saubinettii. Compounds 1, 4, 6, and 7 exhibited antifungal activities against Alternaria solani, with minimal inhibitory concentration (MIC) values from 6.25 to 50 μM. Thus, strain KY-9 represents an untapped source for the development of biological control agents to prevent the infection of pathogenic fungus A. solani.
研究领域:
植物学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2012
·Vol. 12
·期 11
·8266-8275
·
IF 1.563
Wang Yang,Chang Baisong,Yang Wuli
In this work, pH-sensitive nanoparticles based on polyketal copolymer (PK3) were formulated by encapsulating hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic paclitaxel (PTX) into the polymer, respectively. Polyketal PK3 was synthesized by the acetal exchange reaction between
2,2-dimethoxypropane and diols. DOX-loaded nanoparticles were fabricated through a modified double emulsion method and PTX-loaded nanoparticles were obtained by single emulsion method. The results demonstrated that the drug loading content increased with the increase of drug/polymer mass ratio,
and PTX was entrapped into PK3 nanoparticles more effectively due to its hydrophobic character and the single emulsion method. The in vitro release behaviors of the DOX-loaded and PTX-loaded nanoparticles exhibited that both DOX and PTX release were pH-dependent, and the release rate
was much faster in acid environment than that in neutral environment. The cytotoxicity assay of blank nanoparticles indicated that polyketal copolymer (PK3) was biocompatible and suitable as drug vehicle, while PK3 nanoparticle encapsulating DOX or PTX could kill the cancer cells sufficiently
and efficiently. Thus, the pH-sensitive PK3 nanoparticle is a promising carrier for both hydrophilic and hydrophobic anticancer drugs.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED PHYCOLOGY
·
2022
·Vol. 34
·期 3
·1709-1719
·
IF 3.404
Li Jing,Pang Shaojun,Su Li,Shan Tifeng
Phlorotannins are among the most important defensive molecules in kelp. They have been majorly identified in brown algae so far. Type III polyketide synthase (PKS) is regarded as one of the enzymes catalyzing a major step in the biosynthetic pathway of phlorotannins. In this study, a type III PKS gene ( sjPKS1 ) is characterized from the economic brown alga Saccharina japonica sporophyte. It contains 7 exons and 6 introns. The sjPKS1 open reading frame consists of 1245 nucleotides encoding a protein of 414 amino acids. The sjPKS1 are 87%, 83%, and 82% identical to that of Ectocarpus siliculosus , Sargassum binderi , and Sargassum fusiforme at the nucleotide level, respectively. While the amino acid sequences of sjPKS1 share more than 90% identity to that of the three brown algae species. The sjPKS1 expression at 200 µmol photons m −2 s −1 was significantly higher than at 20 and 50 µmol photons m −2 s −1 in sporophytic seedlings, so did the content of soluble phlorotannins inside the plants. Seven motifs in response to light are identified in the 5′ flanking region of sjPKS1 and two potential transcription factors are predicted by screening yeast one-hybrid library.
研究领域:
海洋植物学
·
分子生物学
·
遗传学
✓ 已验证
DOI
高影响因子
BioDesign Research
·
2025
·
IF 4.7
Yuxiang Hong,Yang Gu,Dewei Lin,Zizhao Wu,Wenhao Chen,Tianjian Lu,Pornpatsorn Lertphadungkit,Jingbo Ma,Haili Wang,Bo Zhou,Gil Bar-Sela,Idan Cohen,Peng Xu
Cannabis sativa has long been a cornerstone of both medicinal and cultural practices, with its therapeutic use spanning over 2,700 years. Central to its therapeutic effects are cannabinoids, which interact with the endocannabinoid system to influence various physiological processes such as anxiety, pain, and inflammation. Despite its benefits, cannabinoid production faces challenges and scarcity from plant extraction. This work leverages Yarrowia lipolytica as a platform for cannabinoid biosynthesis. By optimizing precursor supply, engineering biomolecular condensate-like dual prenyltransferase expression and expanding endogenous metabolism with a noncanonical polyketide synthase, we achieved the de novo biosynthesis of various cannabinoid and its analogs. Our engineered Y. lipolytica produced ∼3.5 mg/L of cannabigerolic acid, 18.8 mg/L of orsellinic acid, and 0.5 mg/L of cannabigerorcinic acid. Additionally, CBGA titer reached 15.7 mg/L with olivetolic acid supplement. This work demonstrates Y. lipolytica 's versatility as a promising host for cannabinoid and its analogs production, which opens avenues for further research and medicinal applications.
研究领域:
合成生物学
·
代谢工程
·
植物化学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Energy Materials
·
2021
·
IF 6.024
Yi-cun Zhou,Rui-Ying Bao,Zhengying Liu,Ming-Bo Yang,Wei Yang
It is still a significant challenge to rationally design and delicately process or fabricate anion exchange membranes (AEMs) with high ionic conductivity, good mechanical properties, and sufficient alkaline stability. Here, a polyketone (PK) resin-based AEM was synthesized via the Paal–Knorr reaction and quaternary ammonium reaction, and then processed by electrospinning and hot pressing technologies. In contrast to a quaternized functional polyketone-based polyelectrolyte (QAFPK) fabricated by casting, the electrospun QAFPK shows higher hydroxide conductivity and robust mechanical properties. QAFPK-1-6-E realizes a hydroxide conductivity of 181 mS/cm at 80 °C and a tensile strength of 54 MPa. The microphase structure characterization indicates that the electrospinning process can induce the formation of an excellent ion-conducting structure. The electrospun PK-based AEM displays great application potential in a variety of electrochemical devices under alkaline conditions, such as alkaline anion exchange membrane fuel cells (AAEMFCs).
研究领域:
材料科学
·
化学工程
✓ 已验证
DOI
高影响因子
COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING
·
2020
·
IF 6.444
Yan Yang,Changping Feng,Yichun Zhou,Xiangjun Zha,Ruiying Bao,Kai Ke,Mingbo Yang,Changbin Tan,Wei Yang
A simple and scalable melt compounding strategy is reported to prepare polyketone (POK) nanocomposites with high electrical, dielectric , EMI SE and excellent mechanical properties using poly(vinylidene fluoride) (PVDF) as a carrier of MWCNTs based on the selective distribution and migration of MWCNTs in POK/PVDF blend. The electrical percolation threshold of the POK/PVDF/MWCNT nanocomposites is only a half of that of POK/MWCNT composites due to the homogeneous dispersion of MWCNTs and the double percolation network. The enhanced dielectric performance originates from the interfacial polarization and numerous microcapacitors comprised of MWCNTs within the polymer. The EMI SE performance of the nanocomposites is significantly enhanced due to the selective localization of MWCNTs in the POK phase which provides high conductivity and heterogeneous dielectric media with multiple interfaces. Thus, this study provides possibilities to realize a high-performance polymer nanocomposites and a wider EMI shielding application potentials for POK materials via a composite MWCNTs carrier.
研究领域:
材料科学
·
电气工程
✓ 已验证
产品关联
DOI
高影响因子
Marine Drugs
·
2014
·Vol. 12
·期 4
·1815-1838
·
IF 3.512
Chang-Jing Wu,Chang-Wei Li,Cheng-Bin Cui
AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derivedPenicillium purpurogenumG59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1–7) and two known (8–9) lipopeptides were isolated together with five known polyketides10–14from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A–G (1–7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1′-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay,1–14inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of1–14in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.Keywords:marine-derived fungus;lipopeptide;penicimutalide;Marfey analysis;polyketide;Penicillium purpurogenum;DES mutagenesis
研究领域:
微生物学
·
药物化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2019
·
IF 1.773
Xiao-Wei LUO,Yun LIN,Yong-Jun LU,Xue-Feng ZHOU,Yong-Hong LIU
Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2 ), together with fifteen known compounds (compounds 3–17 ), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11 ) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC 50 being 5.11 ± 0.53 μmol·L −1 , and acted as a noncompetitive inhibitor based on kinetic analysis.
研究领域:
药物化学
·
微生物学
·
有机化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）