在蛋白质工程的基础上,发现和机理性地探索乱交的基转移酶
Huanyu Zhang1, Yanfang Su2, Wei Yuan3
1School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China; State Key Laboratory of Synthetic Biology, Tianjin University, Tianjin 300072, China; Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China.
International journal of biological macromolecules
|January 13, 2025
概括
研究人员对酶进行了工程设计,以创建新的甘油化天然产品,包括一种强大的抗炎化合物. 这项工作推进了用于药物发现的有价值的非天然糖化物的生产.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 自然产品 化学 化学
背景情况:
- 糖基化改变了天然产品 (NP) 的特性和药理活性.
- 葡萄糖类是常见的,但由于有限的基转移酶散乱性和工程挑战,基类是罕见的.
研究的目的:
- 为了设计一种散乱的基转移酶,用于合成各种O-糖化物.
- 开发一种高效的体外途径,用于产生非自然的化NP.
主要方法:
- 对UDP-glycosyltransferases (UGTs) 的遗传学分析,以确定关键的动机.
- 蛋白质工程的一种基转移酶 (M3-2) 的增强基质和糖供体乱交.
- 使用NP和葡萄糖酸开发一个体外合成途径.
主要成果:
- 工程设计的M3-2表现出高的杂交性和O-糖化物合成的选择性.
- 改造的M3-1将糖供体特异性从UDP-Glc切换为UDP-Xyl.
- 通过开发的途径合成了一种新的抗炎性O-糖化物 (10a).
结论:
- 工程UGT能够有效合成各种非自然O-糖化物.
- 开发的 in vitro 途径提供了一条经济的途径,可以获得化NP.
- 这项研究有助于在未来发现和工业生产新型糖化物.
相关概念视频
Mechanical Protein Functions
4.4K
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
4.4K
Gene Conversion
9.2K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
9.2K
Conservative Site-specific Recombination and Phase Variation
5.7K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
5.7K
Exon Recombination
3.1K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.1K
Mismatch Repair
5.4K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.4K
Mechanism of Conjugation
1.6K
Bacterial conjugation is a mechanism of horizontal gene transfer that enables the exchange of genetic material between bacterial cells through direct contact. This process is facilitated by a donor cell carrying a conjugative plasmid, which encodes genes necessary for pilus formation, DNA replication, and transfer. The conjugative plasmid plays a central role in initiating and executing the transfer of genetic material.The tra region of the conjugative plasmid encodes proteins responsible for...
1.6K


