52526-39-3Relevant academic research and scientific papers
Structures and antitumor activities of ten new and twenty known surfactins from the deep-sea bacterium Limimaricola sp. SCSIO 53532
Chen, Min,Chen, Rouwen,Ding, Wenping,Li, Yanqun,Tian, Xinpeng,Yin, Hao,Zhang, Si
, (2022/01/11)
Surfactins are natural biosurfactants with myriad potential applications in the areas of healthcare and environment. However, surfactins were almost exclusively produced by the bacterium Bacillus species in previous reported literatures, together with difficulty in isolating pure monomer, which resulted in making extensive effort to remove duplication and little discovery of new surfactins in recent years. In the present study, the result of Molecular Networking indicated that Limimaricola sp. SCSIO 53532 might well be a potential resource for surfacin-like compounds based on OSMAC strategy. To search for new surfactins with significant biological activity, further study was undertaken on the strain. As a result, ten new surfactins (1–10), along with twenty known surfactins (11–30), were isolated from the ethyl acetate extract of SCSIO 53532. Their chemical structures were established by detailed 1D and 2D NMR spectroscopy, HRESIMS data, secondary ion mass spectrometry (MS/MS) analysis, and chemical degradation (Marfey's method) analysis. Cytotoxic activities of twenty-seven compounds against five human tumor cell lines were tested, and five compounds showed significant antitumor activities with IC50 values less than 10 μM. Furtherly, analysis of structure–activity relationships revealed that the branch of side chain, the esterification of Glu or Asp residue, and the amino acid residue of position 7 possessed a great influence on antitumor activity.
Recreating the natural evolutionary trend in key microdomains provides an effective strategy for engineering of a thermomicrobial N-demethylase
Gu, Zhenghua,Guo, Zitao,Shao, Jun,Shen, Chen,Shi, Yi,Tang, Mengwei,Xin, Yu,Zhang, Liang
, (2022/03/09)
N-demethylases have been reported to remove the methyl groups on primary or secondary amines, which could further affect the properties and functions of biomacromolecules or chemical compounds; however, the substrate scope and the robustness of N-demethylases have not been systematically investigated. Here we report the recreation of natural evolution in key microdomains of the Thermomicrobium roseum sarcosine oxidase (TrSOX), an N-demethylase with marked stability (melting temperature over 100 C) and enantioselectivity, for enhanced substrate scope and catalytic efficiency on -C-N-bonds. We obtained the structure of TrSOX by crystallization and X-ray diffraction (XRD) for the initial framework. The natural evolution in the nonconserved residues of key microdomains—including the catalytic loop, coenzyme pocket, substrate pocket, and entrance site—was then identified using ancestral sequence reconstruction (ASR), and the substitutions that accrued during natural evolution were recreated by site-directed mutagenesis. The single and double substitution variants catalyzed the N-demethylation of N-methyl-L-amino acids up to 1800- and 6000-fold faster than the wild type, respectively. Additionally, these single substitution variants catalyzed the terminal N-demethylation of non-amino-acid compounds and the oxidation of the main chain -C-N- bond to a -C=N- bond in the nitrogen-containing heterocycle. Notably, these variants retained the enantioselectivity and stability of the initial framework. We conclude that the variants of TrSOX are of great potential use in N-methyl enantiomer resolution, main-chain Schiff base synthesis, and alkaloid modification or degradation.
Biosynthesis ofl-alanine fromcis-butenedioic anhydride catalyzed by a triple-enzyme cascadeviaa genetically modified strain
Cui, Ruizhi,Liu, Zhongmei,Yu, Puyi,Zhou, Li,Zhou, Zhemin
, p. 7290 - 7298 (2021/09/28)
In industry,l-alanine is biosynthesized using fermentation methods or catalyzed froml-aspartic acid by aspartate β-decarboxylase (ASD). In this study, a triple-enzyme system was developed to biosynthesizel-alanine fromcis-butenedioic anhydride, which was cost-efficient and could overcome the shortcomings of fermentation. Maleic acid formed bycis-butenedioic anhydride dissolving in water was transformed tol-alanineviafumaric acid andl-asparagic acid catalyzed by maleate isomerase (MaiA), aspartase (AspA) and ASD, respectively. The enzymatic properties of ASD from different origins were investigated and compared, as ASD was the key enzyme of the triple-enzyme cascade. Based on cofactor dependence and cooperation with the other two enzymes, a suitable ASD was chosen. Two of the three enzymes, MaiA and ASD, were recombinant enzymes cloned into a dual-promoter plasmid for overexpression; another enzyme, AspA, was the genomic enzyme of the host cell, in which AspA was enhanced by a T7promoter. Two fumarases in the host cell genome were deleted to improve the utilization of the intermediate fumaric acid. The conversion of whole-cell catalysis achieved 94.9% in 6 h, and the productivity given in our system was 28.2 g (L h)?1, which was higher than the productivity that had been reported. A catalysis-extraction circulation process for the synthesis ofl-alanine was established based on high-density fermentation, and the wastewater generated by this process was less than 34% of that by the fermentation process. Our results not only established a new green manufacturing process forl-alanine production fromcis-butenedioic anhydride but also provided a promising strategy that could consider both catalytic ability and cell growth burden for multi-enzyme cascade catalysis.
Noncovalently Functionalized Commodity Polymers as Tailor-Made Additives for Stereoselective Crystallization
Wan, Xinhua,Wang, Zhaoxu,Ye, Xichong,Zhang, Jie
supporting information, p. 20243 - 20248 (2021/08/09)
Stereoselective inhibition of the nucleation and crystal growth of one enantiomer aided by “tailor-made” polymeric additives is an efficient method to obtain enantiopure compounds. However, the conventional preparation of polymeric additives from chiral monomers are laborious and limited in structures, which impedes their rapid optimization and applicability. Herein, we report a “plug-and-play” strategy to facilitate synthesis by using commercially available achiral polymers as the platform to attach various chiral small molecules as the recognition side-chains through non-covalent interactions. A library of supramolecular polymers made up of two vinyl polymers and six small molecules were applied with seeds in the selective crystallization of seven racemates in different solvents. They showed good to excellent stereoselectivity in yielding crystals with high enantiomeric purities in conglomerates and racemic compound forming systems. This convenient, low-cost modular synthesis strategy of polymeric additives will allow for high-efficient, economical resolution of various racemates on different scales.
Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
supporting information, p. 503 - 517 (2021/03/01)
Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
A plug-and-play chemobiocatalytic route for the one-pot controllable synthesis of biobased C4 chemicals from furfural
Huang, Yi-Min,Lu, Guang-Hui,Zong, Min-Hua,Cui, Wen-Jing,Li, Ning
supporting information, p. 8604 - 8610 (2021/11/16)
Chemobiocatalytic selective transformation is an attractive yet challenging task, due to the incompatibility issues between different types of catalysts. In this work, one-pot, multi-step cascades integrating biocatalysis with organo-, base- and photocatalysis in a plug-and-play fashion were constructed for the controllable synthesis of eight C4 chemicals from furfural. Furfural was converted to 5-hydroxy-2(5H)-furanone (HFO) by sequential biocatalytic oxidation and photooxygenation in phosphate buffer, in >90% yields. Ring opening and concurrent isomerization of HFO to fumaric semialdehyde (FSA) were readily realized under mild conditions by a weakly basic resin (e.g., DVB resin). The versatile intermediate FSA could be oxidized to fumaric acid (FA) using a laccase-2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) system, which was further upgraded to amino acids including l-aspartic acid (l-Asp) and β-alanine (β-Ala) by whole-cell catalysis. Notably, amino acids were obtained from biobased furfural in a one-pot, four-step process with yields of up to 75%, without the isolation of any intermediates. Besides, the scale-up synthesis of l-Asp was demonstrated. This work demonstrates the great potential of the combination of chemo- and biocatalysis for selective furfural valorization.
Comparative study of ASNase immobilization on tannic acid-modified magnetic Fe3O4/SBA-15 nanoparticles to enhance stability and reusability
Noma, Samir Abbas Ali,Ulu, Ahmet,Acet, ?mür,Sanz, Raúl,Sanz-Pérez, Eloy S.,Odaba?i, Mehmet,Ate?, Burhan
, p. 4440 - 4451 (2020/03/27)
In this work, l-asparaginase was immobilized on tannic acid-modified magnetic mesoporous particles. In brief, Fe3O4/SBA-15/tannic acid magnetic particles were synthesized, and their structures and morphologies were fully characterized using various methods. The properties of the free and immobilized enzyme were examined in terms of pH, temperature, thermal stability, storage stability, and reusability. Moreover, the effects of metal ions, inhibitors and organic solvents on the activity of the immobilized enzyme were investigated. Compared to the free enzyme, the immobilized enzyme possessed better tolerance to changes in ambient temperature and pH. Additionally, thermal incubation results showed that the free enzyme lost its activity, while the immobilized enzyme exhibited the opposite behavior. Most strikingly, the immobilized l-asparaginase exhibited a high degree of activity (70%) after being reused 16 times while also demonstrating 71% and 63% storage stability of the initial activity even after 28 days at 4 °C and room temperature, respectively. Together with these results, l-asparaginase was successfully immobilized upon Fe3O4/SBA-15/tannic acid magnetic nanoparticles with improved stability properties. This support holds great potential and opens up a novel perspective for growing applications.
Structure-guided engineering of: Pseudomonas dacunhae l-aspartate β-decarboxylase for l-homophenylalanine synthesis
Zhang, Min,Hu, Pengfei,Zheng, Yu-Cong,Zeng, Bu-Bing,Chen, Qi,Zhang, Zhi-Jun,Xu, Jian-He
, p. 13876 - 13879 (2020/11/18)
Structure-guided engineering of Pseudomonas dacunhael-aspartate β-decarboxylase (AspBDC) resulted in a double mutant (R37A/T382G) with remarkable 15400-fold improvement in specific activity reaching 216 mU mg-1, towards the target substrate 3(R)-benzyl-l-aspartate. A novel strategy for enzymatic synthesis of l-homophenylalanine was developed by using the variant as a biocatalyst affording 75% product yield within 12 h. Our results underscore the potential of engineered AspBDC for the biocatalytic synthesis of pharmaceutically relevant and value added unnatural l-amino acids.
Unique polyhalogenated peptides from the marine sponge Ircinia sp.
Fernández, Rogelio,Bayu, Asep,Hadi, Tri Aryono,Bueno, Santiago,Pérez, Marta,Cuevas, Carmen,Putra, Masteria Yunovilsa
, (2020/08/28)
Two new bromopyrrole peptides, haloirciniamide A (1) and seribunamide A (2), have been isolated from an Indonesian marine sponge of the genus Ircinia collected in the Thousand Islands (Indonesia). The planar structure of both compounds was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of Marfey's method. Compound 1 is the first dibromopyrrole cyclopeptide having a chlorohistidine ring, while compound 2 is a rare peptide possessing a tribromopyrrole ring. Both compounds failed to show significant cytotoxicity against four human tumor cell lines, and neither compound was able to inhibit the enzyme topoisomerase I or impair the interaction between programmed cell death protein PD1 and its ligand, PDL1.
Stalobacin: Discovery of Novel Lipopeptide Antibiotics with Potent Antibacterial Activity against Multidrug-Resistant Bacteria
Matsui, Kouhei,Matsui, Kouhei,Kan, Yukiko,Kikuchi, Junko,Matsushima, Keisuke,Takemura, Miki,Maki, Hideki,Kozono, Iori,Ueda, Taichi,Minagawa, Kazuyuki
supporting information, p. 6090 - 6095 (2020/07/10)
A novel lipopeptide antibiotic, stalobacin I (1), was discovered from a culture broth of an unidentified Gram-negative bacterium. Stalobacin I (1) had a unique chemical architecture composed of an upper and a lower half peptide sequence, which were linked via a hemiaminal methylene moiety. The sequence of 1 contained an unusual amino acid, carnosadine, 3,4-dihydroxyariginine, 3-hydroxyisoleucine, and 3-hydroxyaspartic acid, and a novel cyclopropyl fatty acid. The antibacterial activity of 1 against a broad range of drug-resistant Gram-positive bacteria was much stronger than those of last resort antibiotics such as vancomycin, linezolid, and telavancin (MIC 0.004-0.016 μg/mL). Furthermore, compound 1 induced a characteristic morphological change in Gram-positive and Gram-negative strains by inflating the bacterial cell body. The absolute configuration of a cyclopropyl amino acid, carnosadine, was determined by the synthetic study of its stereoisomers, which was an essential component for the strong activity of 1.
