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Reprogramming the genetic code with flexizymes 用柔性酶重编遗传密码
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-21 DOI: 10.1038/s41570-024-00656-5
Takayuki Katoh, Hiroaki Suga
In the canonical genetic code, the 61 sense codons are assigned to the 20 proteinogenic amino acids. Advancements in genetic code manipulation techniques have enabled the ribosomal incorporation of nonproteinogenic amino acids (npAAs). The critical molecule for translating messenger RNA (mRNA) into peptide sequences is aminoacyl-transfer RNA (tRNA), which recognizes the mRNA codon through its anticodon. Because aminoacyl-tRNA synthetases (ARSs) are highly specific for their respective amino acid–tRNA pairs, it is not feasible to use natural ARSs to prepare npAA-tRNAs. However, flexizymes are adaptable aminoacylation ribozymes that can be used to prepare diverse aminoacyl-tRNAs at will using amino acids activated with suitable leaving groups. Regarding recognition elements, flexizymes require only an aromatic ring in either the leaving group or side chain of the activated amino acid, and the conserved 3′-end CCA of the tRNA. Therefore, flexizymes allow virtually any amino acid to be charged onto any tRNA. The flexizyme system can handle not only l-α-amino acids with side chain modifications but also various backbone-modified npAAs. This Review describes the development of flexizyme variants and discusses their structure and mechanism and their applications in genetic code reprogramming for the synthesis of unique peptides and proteins. Flexizymes can be used to prepare nonproteinogenic aminoacyl-tRNAs (npAA-tRNAs) by activating amino acids with suitable leaving groups, leading to ribosomal incorporation of npAAs by genetic code reprogramming. This enables the ribosomal synthesis of unique peptides and proteins containing various npAAs.
在规范遗传密码中,61 个有义密码子被分配给 20 个蛋白质氨基酸。随着遗传密码操作技术的进步,核糖体中可以加入非蛋白源氨基酸(npAAs)。将信使核糖核酸(mRNA)翻译成肽序列的关键分子是氨基酰转移核糖核酸(tRNA),它通过反密码子识别 mRNA 密码子。由于氨基酰-tRNA 合成酶(ARSs)对各自的氨基酸-tRNA 对具有高度特异性,因此使用天然 ARSs 制备 npAA-tRNAs 是不可行的。然而,柔性酶是一种适应性很强的氨基酰化核糖酶,可以利用被适当离去基团激活的氨基酸随意制备各种氨基酰-tRNA。在识别元件方面,柔性酶只需要活化氨基酸的离去基团或侧链中的芳香环,以及 tRNA 的保守 3′ 端 CCA。因此,柔性酶几乎可以将任何氨基酸加载到任何 tRNA 上。柔性酶系统不仅能处理侧链修饰的 l-α 氨基酸,还能处理各种骨架修饰的 npAA。本综述介绍了柔性酶变体的发展,讨论了它们的结构和机理,以及它们在遗传密码重编程合成独特多肽和蛋白质中的应用。
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引用次数: 0
2D magnets filled with lithium 充满锂的二维磁铁
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-10 DOI: 10.1038/s41570-024-00660-9
Liang Mei, Ruijie Yang
Room-temperature magnetism is challenging for 2D materials as they tend to lose their magnetic order at increasing temperatures. Now, researchers have achieved room temperature magnetism in lithium-intercalated chromium iodide.
室温磁性对于二维材料来说具有挑战性,因为它们在温度升高时往往会失去磁性。现在,研究人员在锂迭合碘化铬中实现了室温磁性。
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引用次数: 0
Asymmetric phase-transfer catalysis 不对称相转移催化。
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-09 DOI: 10.1038/s41570-024-00642-x
Hyo-Jun Lee, Keiji Maruoka
Over the past three decades, chiral phase-transfer catalysts (PTCs) have emerged as highly successful organocatalysts in a diverse range of asymmetric reactions. A substantial number of chiral PTCs have now already been discovered and utilized in dependable routes to enantioenriched products. These extend beyond the classical cationic PTCs with the emergence of anionic phase-transfer catalysis and hydrogen-bonding phase-transfer catalysis providing new asymmetric synthetic approaches. Nevertheless, the application level of chiral PTCs in both academic and industrial processes is below our expectation. This Review highlights the notable advances in chiral PTCs, including challenges, limitations and efforts to overcome them. Following this, the potential for sustainable chiral PTCs is described with a focus on using photocatalysed, flow and electrochemical synthesis. Chiral phase-transfer catalysts are practical and powerful organocatalysts for asymmetric synthesis. This Review illustrates notable recent advances of chiral phase-transfer catalysts, including challenges, limitations and potential solutions, as well as future opportunities to improve sustainability.
在过去的三十年中,手性相转移催化剂(PTC)已成为各种不对称反应中非常成功的有机催化剂。现在已经发现了大量的手性 PTC,并将其用于获得对映体富集产物的可靠途径。随着阴离子相转移催化和氢键相转移催化的出现,这些催化剂已超越了经典的阳离子相转移催化,提供了新的不对称合成方法。尽管如此,手性 PTC 在学术和工业过程中的应用水平仍低于我们的预期。本综述重点介绍手性 PTC 的显著进展,包括挑战、局限性和克服这些挑战的努力。随后,介绍了可持续手性 PTC 的潜力,重点是光催化、流动和电化学合成。
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引用次数: 0
Accessing monomers from lignin through carbon–carbon bond cleavage 通过碳-碳键裂解从木质素中获取单体
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-04 DOI: 10.1038/s41570-024-00652-9
Chad T. Palumbo, Erik T. Ouellette, Jie Zhu, Yuriy Román-Leshkov, Shannon S. Stahl, Gregg T. Beckham
Lignin, the heterogeneous aromatic macromolecule found in the cell walls of vascular plants, is an abundant feedstock for the production of biochemicals and biofuels. Many valorization schemes rely on lignin depolymerization, with decades of research focused on accessing monomers through C–O bond cleavage, given the abundance of β–O–4 bonds in lignin and the large number of available C–O bond cleavage strategies. Monomer yields are, however, invariably lower than desired, owing to the presence of recalcitrant C–C bonds whose selective cleavage remains a major challenge in catalysis. In this Review, we highlight lignin C–C cleavage reactions, including those of linkages arising from biosynthesis (β–1, β–5, β–β and 5–5) and industrial processing (5–CH2–5 and α–5). We examine multiple approaches to C–C cleavage, including homogeneous and heterogeneous catalysis, photocatalysis and biocatalysis, to identify promising strategies for further research and provide guidelines for definitive measurements of lignin C–C bond cleavage. To date, monomer yields from lignin are limited to those attainable through C–O bond cleavage. Cleaving C–C bonds often leads to deleterious product degradation and low monomer yields. Herein we review lignin C–C cleavage reports and advocate for a standardized reporting of yields.
木质素是维管植物细胞壁中的异质芳香族大分子,是生产生物化学品和生物燃料的丰富原料。由于木质素中含有大量的 β-O-4 键,而且有大量可用的 C-O 键裂解策略,因此几十年来的研究重点都是通过 C-O 键裂解来获得单体。然而,由于存在难处理的 C-C 键,其选择性裂解仍是催化过程中的一大挑战,因此单体产量总是低于预期。在本综述中,我们将重点介绍木质素 C-C 裂解反应,包括生物合成(β-1、β-5、β-β 和 5-5)和工业加工(5-CH2-5 和 α-5)过程中产生的连接。我们研究了 C-C 裂解的多种方法,包括均相催化和异相催化、光催化和生物催化,以确定有前途的进一步研究策略,并为木质素 C-C 键裂解的明确测量提供指导。
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引用次数: 0
Secrets from a spin-out success story 成功分拆的秘诀
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-01 DOI: 10.1038/s41570-024-00634-x
Stephanie Greed
Ahead of his 85th birthday, Graham Richards discussed his life in science and its intersection with industry. From a mix-up that led to him reading chemistry at the University of Oxford rather than physics, Richards later became the head of the chemistry department and co-founded Oxford Molecular Plc.
在他 85 岁生日之前,格雷厄姆-理查兹(Graham Richards)讨论了他的科学人生及其与工业的交集。理查兹在牛津大学读的是化学而不是物理,后来他成为了化学系主任,并共同创立了牛津分子公司。
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引用次数: 0
Ni-catalysed remote C(sp3)–H functionalization using chain-walking strategies 镍催化的远程 C(sp3)-H 功能化(使用 "遛链 "策略
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-10-01 DOI: 10.1038/s41570-024-00649-4
Ciro Romano, Ruben Martin
The dynamic translocation of a metal catalyst along an alkyl side chain — often coined as ‘chain-walking’ — has opened new retrosynthetic possibilities that enable functionalization at unactivated C(sp3)–H sites. The use of nickel complexes in chain-walking strategies has recently gained considerable momentum owing to their versatility for forging sp3 architectures and their redox promiscuity that facilitates both one-electron or two-electron reaction manifolds. This Review discusses the relevance and impact that these processes might have in synthetic endeavours, including mechanistic considerations when appropriate. Particular emphasis is given to the latest discoveries that leverage the potential of Ni-catalysed chain-walking scenarios for tackling transformations that would otherwise be difficult to accomplish, including the merger of chain-walking with other new approaches such as photoredox catalysis or electrochemical activation. Ni-catalysed chain-walking blossomed as an effective synthetic tool to functionalize C(sp3)–H bonds in hydrocarbon chains. This Review provides a detailed overview of the most recent advances in this field, focusing on site-selective and regioselective manipulations at previously out-of-reach C(sp3)–H sites.
金属催化剂沿烷基侧链的动态转移--通常被称为 "链行"--开辟了新的逆合成可能性,使未活化的 C(sp3)-H 位点得以功能化。由于镍络合物在形成 sp3 结构方面的多功能性,以及其氧化还原性可促进单电子或双电子反应歧管,因此在链烷基化策略中使用镍络合物最近获得了相当大的发展势头。本综述讨论了这些过程在合成工作中可能产生的相关性和影响,包括适当时的机理考虑。其中特别强调了利用镍催化链式反应的潜力来解决原本难以实现的转化问题的最新发现,包括链式反应与光氧化催化或电化学活化等其他新方法的结合。
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引用次数: 0
On the aqueous origins of the condensation polymers of life 生命缩合聚合物的水性起源。
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-27 DOI: 10.1038/s41570-024-00648-5
Daniel Whitaker, Matthew W. Powner
Water is essential for life as we know it, but it has paradoxically been considered inimical to the emergence of life. Proteins and nucleic acids have sustained evolution and life for billions of years, but both are condensation polymers, suggesting that their formation requires the elimination of water. This presents intrinsic challenges at the origins of life, including how condensation polymer synthesis can overcome the thermodynamic pressure of hydrolysis in water and how nucleophiles can kinetically outcompete water to yield condensation products. The answers to these questions lie in balancing thermodynamic activation and kinetic stability. For peptides, an effective strategy is to directly harness the energy trapped in prebiotic molecules, such as nitriles, and avoid the formation of fully hydrolysed monomers. In this Review, we discuss how chemical energy can be built into precursors, retained, and released selectively for polymer synthesis. Looking to the future, the outstanding goals include how nucleic acids can be synthesized, avoiding the formation of fully hydrolysed monomers and what caused information to flow from nucleic acids to proteins. Water is essential for life but paradoxically considered detrimental to the origins of life. Here, we discuss whether avoiding hydrolysed monomers and exploiting the chemical energy in prebiotic precursors may hold the missing key to unlocking biopolymer synthesis.
水对于我们所知的生命来说是必不可少的,但矛盾的是,水却被认为与生命的出现背道而驰。蛋白质和核酸维持了数十亿年的进化和生命,但它们都是缩聚聚合物,这表明它们的形成需要消除水。这给生命起源带来了内在挑战,包括缩合聚合物合成如何克服水中水解的热力学压力,以及亲核物如何在动力学上与水竞争以产生缩合产物。这些问题的答案在于平衡热力学活化和动力学稳定性。对于多肽来说,有效的策略是直接利用腈类等前生物分子中蕴藏的能量,避免形成完全水解的单体。在本综述中,我们将讨论如何在聚合物合成过程中将化学能植入前体、保留并有选择性地释放出来。展望未来,突出的目标包括如何合成核酸,避免形成完全水解的单体,以及是什么导致信息从核酸流向蛋白质。
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引用次数: 0
The current utility and future potential of multiborylated alkanes 多溴化烷烃的当前用途和未来潜力
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-26 DOI: 10.1038/s41570-024-00650-x
Kane A. C. Bastick, Dean D. Roberts, Allan J. B. Watson
Organoboron chemistry has become a cornerstone of modern synthetic methodology. Most of these reactions use an organoboron starting material that contains just one C(sp2)–B or C(sp3)–B bond; however, there has been a recent and accelerating trend to prepare multiborylated alkanes that possess two or more C(sp3)–B bonds. This is despite a lack of general reactivity, meaning many of these compounds currently offer limited downstream synthetic value. This Review summarizes recent advances in the exploration of multiborylated alkanes, including a discussion on how these products may be elaborated in further synthetic manipulations. Monoborylated alkanes display diverse reactivity and broad application; however, despite an increasing number of approaches to access them, multiborylated alkanes have yet to realize their synthetic potential. This Review highlights the current state-of-the-art in approaches to and synthetic applications of multiborylated alkanes.
有机硼化学已成为现代合成方法的基石。这些反应大多使用仅含有一个 C(sp2)-B 或 C(sp3)-B 键的有机硼起始材料;然而,最近制备具有两个或更多 C(sp3)-B 键的多硼化烷烃的趋势正在加速发展。尽管缺乏一般反应性,这意味着许多此类化合物目前的下游合成价值有限。本综述总结了在探索多硼烷方面的最新进展,包括讨论如何在进一步的合成操作中对这些产品进行阐述。
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引用次数: 0
Reviving antibiotic power 重振抗生素威力
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-24 DOI: 10.1038/s41570-024-00655-6
Sammer Marzouk, Dang Nguyen, Cameron Sabet
Inhibiting a signal transducer, which kicks off the production of β-lactamase in response to the presence of an antibiotic, shuts down resistance and makes β-lactam antibiotics effective once more.
抑制信号转导器(它会在抗生素存在时启动 β-内酰胺酶的产生)可以抑制抗药性,使 β-内酰胺类抗生素再次有效。
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引用次数: 0
The Not Voodoo website after twenty dynamic years Not Voodoo 网站历经二十年的蓬勃发展。
IF 38.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-24 DOI: 10.1038/s41570-024-00644-9
Alison J. Frontier
2024 marks twenty years of the educational website Not Voodoo: Demystifying Synthetic Organic Chemistry — a fount of knowledge for organic chemistry laboratory techniques, with tips and tricks for both beginning research students and advanced experimentalists. 
2024 年是教育网站 "非巫术"(Not Voodoo)成立二十周年:解密合成有机化学--有机化学实验室技术的知识宝库,为初学研究的学生和高级实验者提供技巧和窍门;
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引用次数: 0
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Nature reviews. Chemistry
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