共查询到20条相似文献,搜索用时 15 毫秒
1.
Gina L. Morgan Prof. Bo Li 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(48):21571-21575
The Pseudomonas virulence factor (pvf) operon is essential for the biosynthesis of two very different natural product scaffolds: the (dihydro)pyrazine-N-oxides and the diazeniumdiolate, valdiazen. PvfB is a member of the non-heme diiron N-oxygenase enzyme family that commonly convert anilines to their nitroaromatic counterparts. In contrast, we show that PvfB catalyzes N-oxygenation of the α-amine of valine, first to the hydroxylamine and then the nitroso, while linked to the carrier protein of PvfC. PvfB modification of PvfC-tethered valine was observed directly by protein NMR spectroscopy, establishing the intermediacy of the hydroxylamine. This work reveals a central role for PvfB in the biosynthesis of (dihydro)pyrazine-N-oxides and valdiazen. 相似文献
2.
Francesco De Angelis Rosario Nicoletti Nicoletta Spreti Franca Verì 《Angewandte Chemie (International ed. in English)》1999,38(9):1283-1285
A strictly coordinate sequence of radical and ionic steps appears to be the mechanism by which oligolignols are generated. A synthetic lignin was produced under micellar conditions [Eq. (1)], and the beginning of the polymerization process was studied by electrospray ionization mass spectrometry. CTA=cetyltrimethylammonium ion 相似文献
3.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2018,130(23):6896-6901
Oxyvinylglycines are a family of nonproteinogenic amino acids featuring an essential vinyl ether conferring mechanism‐based inhibition of pyridoxal phosphate enzymes. The gene clusters for a few oxyvinylglycines are known, yet the biosynthetic origin of the vinyl ether is elusive. The in vitro biosynthesis of methoxyvinylglycine or l ‐2‐amino‐4‐methoxy‐trans‐3‐butenoic acid (AMB) is reported. It is shown that AMB is made from glutamate as an alanyl‐AMB dipeptide and the rationale is provided for the N‐term Ala. Using a chemical capture method, the order and timing of the modifications on non‐ribosomal peptide synthetase (NRPS)‐bound substrates was determined, including a cryptic hydroxylation of the Glu β‐carbon. Eliminating this hydroxy group likely generates a key α,β‐dehydroamino acid intermediate that facilitates decarboxylation. This work sheds light on vinyl ether biosynthesis and uncovers new NRPS chemistry. 相似文献
4.
Jeroen S. Dickschat 《Angewandte Chemie (International ed. in English)》2019,58(45):15964-15976
This Minireview summarises recent developments in the biosynthesis of diterpenes by diterpene synthases in bacteria. It is structured by the class of enzyme involved in the first committed step towards diterpenes, starting with type I diterpene synthases, followed by type II enzymes and the more recently discovered UbiA‐related diterpene synthases. A special emphasis lies on the reaction mechanisms of diterpene synthases that convert simple linear precursors through cationic cascades into structurally complex, usually polycyclic carbon skeletons with multiple stereogenic centres. A further main focus of this Minireview is a discussion of how these mechanisms can be unravelled. Downstream modifications to bioactive molecules are also covered. 相似文献
5.
In Vitro Reconstitution of OxyC Activity Enables Total Chemoenzymatic Syntheses of Vancomycin Aglycone Variants 下载免费PDF全文
Clarissa C. Forneris Prof. Dr. Mohammad R. Seyedsayamdost 《Angewandte Chemie (International ed. in English)》2018,57(27):8048-8052
The bioactivity of vancomycin is enabled by three aromatic crosslinks, the biosynthesis of which has been an active area of investigation for two decades. Two cytochrome P450 enzymes, OxyB and OxyA, have been shown to introduce bisaryl ether linkages with the help of a so‐called X‐domain. The final crosslink, however, a biaryl bond thought to be installed by OxyC, has remained elusive. We report the in vitro reconstitution of the OxyC reaction and formation of the first carbon–carbon crosslink in any glycopeptide antibiotic. Using a cascade sequence, in which the peptide substrate was incubated with the Oxy enzymes in turn, we completed the chemoenzymatic synthesis of a vancomycin aglycone variant. This approach was also used to generate a new analogue carrying a thioamide linkage at residue 4, a precursor to the amidine derivative, which is effective against vancomycin‐resistant pathogens. Our results set the stage for creating therapeutic vancomycin derivatives by using the native metalloenzymes. 相似文献
6.
Wen Zhang Qian-Yu Zhang Jian-Jun Wang Le-Le Zhang Zhen-Zhen Dong 《Molecules (Basel, Switzerland)》2022,27(11)
Bacterial cellulose (BC) is well known as a high-performance dietary fiber. This study investigates the adsorption capacity of BC for cholesterol, sodium cholate, unsaturated oil, and heavy metal ions in vitro. Further, a hyperlipidemia mouse model was constructed to investigate the effects of BC on lipid metabolism, antioxidant levels, and intestinal microflora. The results showed that the maximum adsorption capacities of BC for cholesterol, sodium cholate, Pb2+ and Cr6+ were 11.910, 16.149, 238.337, 1.525 and 1.809 mg/g, respectively. Additionally, BC reduced the blood lipid levels, regulated the peroxide levels, and ameliorated the liver injury in hyperlipidemia mice. Analysis of the intestinal flora revealed that BC improved the bacterial community of intestinal microflora in hyperlipidemia mice. It was found that the abundance of Bacteroidetes was increased, while the abundance of Firmicutes and Proteobacteria was decreased at the phylum level. In addition, increased abundance of Lactobacillus and decreased abundance of Lachnospiraceae and Prevotellaceae were obtained at the genus level. These changes were supposed to be beneficial to the activities of intestinal microflora. To conclude, the findings prove the role of BC in improving lipid metabolism in hyperlipidemia mice and provide a theoretical basis for the utilization of BC in functional food. 相似文献
7.
Leader Peptide‐Free In Vitro Reconstitution of Microviridin Biosynthesis Enables Design of Synthetic Protease‐Targeted Libraries 下载免费PDF全文
Emmanuel Reyna‐González Bianca Schmid Dr. Daniel Petras Prof. Dr. Roderich D. Süssmuth Prof. Dr. Elke Dittmann 《Angewandte Chemie (International ed. in English)》2016,55(32):9398-9401
Microviridins are a family of ribosomally synthesized and post‐translationally modified peptides with a highly unusual architecture featuring non‐canonical lactone as well as lactam rings. Individual variants specifically inhibit different types of serine proteases. Here we have established an efficient in vitro reconstitution approach based on two ATP‐grasp ligases that were constitutively activated using covalently attached leader peptides and a GNAT‐type N‐acetyltransferase. The method facilitates the efficient in vitro one‐pot transformation of microviridin core peptides to mature microviridins. The engineering potential of the chemo‐enzymatic technology was demonstrated for two synthetic peptide libraries that were used to screen and optimize microviridin variants targeting the serine proteases trypsin and subtilisin. Successive analysis of intermediates revealed distinct structure–activity relationships for respective target proteases. 相似文献
8.
9.
Hongjuan Si Honglin Luo Guangyao Xiong Zhiwei Yang Sudha R. Raman Ruisong Guo Yizao Wan 《Macromolecular rapid communications》2014,35(19):1706-1711
Graphene oxide–bacterial cellulose (GO/BC) nanocomposite hydrogels with well‐dispersed GO in the network of BC are successfully developed using a facile one‐step in situ biosynthesis by adding GO suspension into the culture medium of BC. During the biosynthesis process, the crystallinity index of BC decreases and GO is partially reduced. The experimental results indicate that GO nanosheets are uniformly dispersed and well‐bound to the BC matrix and that the 3D porous structure of BC is sustained. This is responsible for efficient load transfer between the GO reinforcement and BC matrix. Compared with the pure BC, the tensile strength and Young's modulus of the GO/BC nanocomposite hydrogel containing 0.48 wt% GO are significantly improved by about 38 and 120%, respectively. The GO/BC nanocomposite hydrogels are promising as a new material for tissue engineering scaffolds.
10.
M.Sc. Janine Antosch Dipl.‐Chem. Françoise Schaefers Dr. Tobias A. M. Gulder 《Angewandte Chemie (International ed. in English)》2014,53(11):3011-3014
Polycyclic tetramate macrolactams (PTMs) are a family of biomedically promising natural products with challenging molecular frameworks. Despite these interesting properties, so far only relatively little is known about the biosynthetic origin of PTMs, in particular concerning the mechanism by which their ring systems are formed. Herein we present the first insights into these processes by using the biosynthesis of ikarugamycin as an example. This has been facilitated by the first heterologous expression of a PTM biosynthetic gene cluster in Escherichia coli. With this approach it will not only become possible to mechanistically investigate already known PTM biosynthetic pathways in more detail in the future, but also to interrogate cryptic PTM biosynthetic pathways chemically and biochemically. 相似文献
11.
Emad M. Abdallah Abueliz Modwi Samiah H. Al-Mijalli Afrah E. Mohammed Hajo Idriss Abdulkader Shaikh Omar Mohamed Afifi Ammar AL-Farga Khang Wen Goh Long Chiau Ming 《Molecules (Basel, Switzerland)》2022,27(23)
In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria’s growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings. 相似文献
12.
Minglong Liu Vito Thijssen Dr. Seino A. K. Jongkees 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(49):22054-22058
Genetic code reprogramming is a powerful approach to controlled protein modification. A remaining challenge, however, is the generation of vacant codons. We targeted the initiation machinery of E. coli, showing that restriction of the formyl donor or inhibition of the formyl transferase during in vitro translation is sufficient to prevent formylation of the acylated initiating tRNA and thereby create a vacant initiation codon that can be reprogrammed by exogenously charged tRNA. Our approach conveniently generates peptides and proteins tagged N-terminally with non-canonical functional groups at up to 99 % reprogramming efficiency, in combination with decoding the AUG elongation codons either with native methionine or with further reprogramming with azide- and alkyne-containing cognates. We further show macrocyclization and intermolecular modifications with these click handles, thus emphasizing the applicability of our method to current challenges in peptide and protein chemistry. 相似文献
13.
Nagendra Prasad Kurumbang Kwangkyoung Liou Jae Kyung Sohng 《Applied biochemistry and biotechnology》2011,163(3):373-382
Ribostamycin is a 4,5-disubstituted 2-deoxystreptamine (DOS)-containing aminoglycoside antibiotics and naturally produced
by Streptomyces ribosidificus ATCC 21294. It is also an intermediate in the biosynthesis of butirosin and neomycin. In the biosynthesis of ribostamycin,
DOS is glycosylated to generate paromamine which is converted to neamine by successive dehydrogenation followed by amination,
and finally ribosylation of neamine gives ribostamycin. Here, we report the biosynthesis of 6′-deamino-6′-hydroxyribostamycin
(a ribostamycin derivative or pseudoribostamycin) in Streptomyces venezuelae YJ003 by reconstructing gene cassettes for direct ribosylation of paromamine. A trace amount of pseudoribostamycin was detected
with ribostamycin in the isolates of ribostamycin cosmid heterologously expressed in Streptomyces lividans TK24. It has also indicated that the ribosyltransferase can accept both neamine and paromamine. Thus, the present in vivo
modification of ribostamycin could be useful for the production of hybrid compounds to defend against bacterial resistance
to aminoglycosides. 相似文献
14.
Kyle L. Dunbar Maria Dell Evelyn M. Molloy Florian Kloss Christian Hertweck 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(37):13148-13152
Thioamide‐containing nonribosomal peptides (NRPs) are exceedingly rare. Recently the biosynthetic gene cluster for the thioamidated NRP antibiotic closthioamide (CTA) was reported, however, the enzyme responsible for and the timing of thioamide formation remained enigmatic. Here, genome editing, biochemical assays, and mutational studies are used to demonstrate that an Fe‐S cluster containing member of the adenine nucleotide α‐hydrolase protein superfamily (CtaC) is responsible for sulfur incorporation during CTA biosynthesis. However, unlike all previously characterized members, CtaC functions in a thiotemplated manner. In addition to prompting a revision of the CTA biosynthetic pathway, the reconstitution of CtaC provides the first example of a NRP thioamide synthetase. Finally, CtaC is used as a bioinformatic handle to demonstrate that thioamidated NRP biosynthetic gene clusters are more widespread than previously appreciated. 相似文献
15.
Olivia Schimming Victoria L. Challinor Nicholas J. Tobias Hlne Adihou Peter Grün Laura Pschel Christian Richter Harald Schwalbe Helge B. Bode 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2015,127(43):12893-12896
Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non‐ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram‐negative and Gram‐positive bacteria indicates an important biological function in bacteria. 相似文献
16.
Olivia Schimming Dr. Victoria L. Challinor Dr. Nicholas J. Tobias Dr. Hélène Adihou Peter Grün Laura Pöschel Dr. Christian Richter Prof. Dr. Harald Schwalbe Prof. Dr. Helge B. Bode 《Angewandte Chemie (International ed. in English)》2015,54(43):12702-12705
Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non‐ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram‐negative and Gram‐positive bacteria indicates an important biological function in bacteria. 相似文献
17.
Shaheen Tharwat I. El-Gamal Mamdouh S. Desouky Said E. Hassan Saad El Din Alemam Ahmed M. 《Journal of Cluster Science》2022,33(6):2735-2751
Journal of Cluster Science - New facile way for production of antimicrobial wound healing dress was achieved using freshly fabricated bacterial cellulose (BNC) decorated with in situ formed silver... 相似文献
18.
Mohamed I. Hassan Benjamin R. Lundgren Michael Chaumun Dennis M. Whitfield Brady Clark Ian C. Schoenhofen Christopher N. Boddy 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2016,128(39):12197-12200
Legionaminic acid, Leg5,7Ac2, a nonulosonic acid like 5‐acetamido neuraminic acid (Neu5Ac, sialic acid), is found in cell surface glycoconjugates of bacteria including the pathogens Campylobacter jejuni, Acinetobacter baumanii and Legionella pneumophila. The presence of Leg5,7Ac2 has been correlated with virulence in humans by mechanisms that likely involve subversion of the host's immune system or interactions with host cell surfaces due to its similarity to Neu5Ac. Investigation into its role in bacterial physiology and pathogenicity is limited as there are no effective sources of it. Herein, we construct a de novo Leg5,7Ac2 biosynthetic pathway by combining multiple metabolic modules from three different microbial sources (Saccharomyces cerevisiae, C. jejuni, and L. pneumophila). Over‐expression of this de novo pathway in Escherichia coli that has been engineered to lack two native catabolic pathways, enables significant quantities of Leg5,7Ac2 (≈120 mg L−1 of culture broth) to be produced. Pure Leg5,7Ac2 could be isolated and converted into CMP‐activated sugar for biochemical applications and a phenyl thioglycoside for chemical synthesis applications. This first total biosynthesis provides an essential source of Leg5,7Ac2 enabling study of its role in prokaryotic and eukaryotic glycobiology. 相似文献
19.
Mohamed I. Hassan Benjamin R. Lundgren Michael Chaumun Dennis M. Whitfield Brady Clark Ian C. Schoenhofen Christopher N. Boddy 《Angewandte Chemie (International ed. in English)》2016,55(39):12018-12021
Legionaminic acid, Leg5,7Ac2, a nonulosonic acid like 5‐acetamido neuraminic acid (Neu5Ac, sialic acid), is found in cell surface glycoconjugates of bacteria including the pathogens Campylobacter jejuni, Acinetobacter baumanii and Legionella pneumophila. The presence of Leg5,7Ac2 has been correlated with virulence in humans by mechanisms that likely involve subversion of the host's immune system or interactions with host cell surfaces due to its similarity to Neu5Ac. Investigation into its role in bacterial physiology and pathogenicity is limited as there are no effective sources of it. Herein, we construct a de novo Leg5,7Ac2 biosynthetic pathway by combining multiple metabolic modules from three different microbial sources (Saccharomyces cerevisiae, C. jejuni, and L. pneumophila). Over‐expression of this de novo pathway in Escherichia coli that has been engineered to lack two native catabolic pathways, enables significant quantities of Leg5,7Ac2 (≈120 mg L?1 of culture broth) to be produced. Pure Leg5,7Ac2 could be isolated and converted into CMP‐activated sugar for biochemical applications and a phenyl thioglycoside for chemical synthesis applications. This first total biosynthesis provides an essential source of Leg5,7Ac2 enabling study of its role in prokaryotic and eukaryotic glycobiology. 相似文献