- Expanding the Structural Diversity of Protein Building Blocks with Noncanonical Amino Acids Biosynthesized from Aromatic Thiols
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Incorporation of structurally novel noncanonical amino acids (ncAAs) into proteins is valuable for both scientific and biomedical applications. To expand the structural diversity of available ncAAs and to reduce the burden of chemically synthesizing them, we have developed a general and simple biosynthetic method for genetically encoding novel ncAAs into recombinant proteins by feeding cells with economical commercially available or synthetically accessible aromatic thiols. We demonstrate that nearly 50 ncAAs with a diverse array of structures can be biosynthesized from these simple small-molecule precursors by hijacking the cysteine biosynthetic enzymes, and the resulting ncAAs can subsequently be incorporated into proteins via an expanded genetic code. Moreover, we demonstrate that bioorthogonal reactive groups such as aromatic azides and aromatic ketones can be incorporated into green fluorescent protein or a therapeutic antibody with high yields, allowing for subsequent chemical conjugation.
- Wang, Yong,Chen, Xiaoxu,Cai, Wenkang,Tan, Linzhi,Yu, Yutong,Han, Boyang,Li, Yuxuan,Xie, Yuanzhe,Su, Yeyu,Luo, Xiaozhou,Liu, Tao
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supporting information
p. 10040 - 10048
(2021/03/26)
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- Dynamic Kinetic Resolution for Asymmetric Synthesis of L-Noncanonical Amino Acids from D-Ser Using Tryptophan Synthase and Alanine Racemase
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L-Ser is often used to synthesize some significant l-noncanonical α-amino acids(l-ncAAs), which are the prevalent intermediates and precursors for functional synthetic compounds. In this study, threonine aldolase from Escherichia coli k-12 MG1655 has been used to synthesize l-Ser. In contrast to the maximum catalytic capacity (20 g/L) for l-threonine aldolase(LTA), d-Ser was synthesized with high yield (240 g/L) from cheap Gly and paraformaldehyde using d-threonine aldolase (DTA) from Arthrobacter sp ATCC. In order to fully utilize d-Ser and expand the resource of l-Ser, a dynamic kinetic resolution system was constructed to convert d/dl-Ser to l-Ser through combining alanine racemase (Alr) from Bacillus subtilis with l-tryptophan synthase (TrpS) from Escherichia coli k-12 MG1655, and l-ncAAs including l-Trp and l-Cys derivatives were synthesized with excellent enantioselectivity and in high yields. The results indicated l-ncAAs could be efficiently synthesized from d-Ser using this original and green dynamic kinetic resolution system, and the reliable l-Ser resource has been established from simple and achiral substrates.
- Yu, Jinhai,Li, Jing,Gao, Xia,Zeng, Shuiyun,Zhang, Hongjuan,Liu, Junzhong,Jiao, Qingcai
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p. 6618 - 6625
(2019/11/03)
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- Unnatural amino acid synthesis by thermostable O-phospho-L-serine sulfhydrylase from hyperthermophilic archaeon Aeropyrum pernix K1
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O-Acetyl-L-serine sulfhydrylase (OASS) from plants and bacteria synthesizes cysteine and unnatural amino acids that are important building blocks for active pharmaceuticals and agrochemicals. A thermostable O-phospho-L-serine sulfhydrylase from hyperthermophilic archaeon Aeropyrum pernix K1 (OPSSAp) exhibits a function similar to OASS. In the present study, we examined the synthesis of various unnatural amino acids using OPSSAp and demonstrated OPSSAp could efficiently synthesize various sulfur-containing amino acids. OPSSAp would be useful for industrial production of biologically important unnatural amino acids.
- Nakamura, Takashi,Kunimoto, Kohei,Yuki, Toru,Ishikawa, Kazuhiko
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supporting information
p. 1789 - 1792
(2017/11/23)
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- A biomimetic approach to lanthionines
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The asymmetric sulfa-Michael additions of appropriately protected l- and d-cysteine derivatives to new chiral dehydroamino acid derivatives have been developed as key steps in the synthesis of biologically important cysteine derivatives, such as lanthionine (Lan) and β-methyllanthionine (MeLan), which are unusual bis-α-amino acids found in the emerging lantibiotics such as nisin.
- Aydillo, Carlos,Avenoza, Alberto,Busto, Jesus H.,Jimenez-Oses, Gonzalo,Peregrina, Jesus M.,Zurbano, Maria M.
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supporting information; experimental part
p. 334 - 337
(2012/03/26)
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- Processes for producing β-halogeno-α-amino-carboxylic acids and phenylcysteine derivatives and intermediates thereof
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An industrially advantageous method of producing β-halogeno-α-aminocarboxylic acids is provided. Methods are also provided of producing optically active N-protected-S-phenylcysteines having high optical purity and of intermediates thereof, respectively, in which the above production method is utilized. A method of producing β-halogeno-α-aminocarboxylic acids or salts thereof is disclosed which comprises halogenating the hydroxyl group of a β-hydroxy-α-aminocarboxylic acid (in which the basicity of the amino group in α-position is not masked by the presence of a substituent on said amino group) or a salt thereof with an acid with a halogenating agent. A method of producing optically active N-protected-S-phenylcysteines represented by the general formula (3) or salts thereof is further disclosed which comprises applying the above production method to optically active serine or a salt thereof and then carrying out treatment with an amino-protecting agent and reaction with thiophenol under a basic condition.
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Page column 20
(2010/01/31)
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- Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I
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Acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14, from porcine kidney and the fungus Aspergillus) is broadly applicable enzymatic catalyst for the kinetic resolution of unnatural and rarely occuring α-amino acids.Its enantioselectivity for the hydrolysis of N-acyl L-α-amino acids is nearly absolute, yet it accepts substrates having a wide range of structure and functionality.This paper reports the initial rates of enzyme-catalyzed hydrolysis of over 50 N-acyl amino acids and analogues, the stabilities of the enzymes in aqueous and aqueous/organic solutions, and the effects of different acyl groups and metal ions on the rates of enzymatic hydrolysis.Eleven α-amino and α-methyl α-amino acids were resolved on a 2-29-g scale.Crude L- and D-amino acid products had generally >90percent ee.The utility of resolved amino acids as chiral synthons was illustrated by the preparation of (R)- and (S)-1-butene oxide and the diastereoselective (cis:trans, 7-8:1) iodolactonization of three 2-amino-4-alkenoic acid derivatives.
- Chenault, H. Keith,Dahmer, Juergen,Whitesides, George M.
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p. 6354 - 6364
(2007/10/02)
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- ASYMMERTIC SYNTHESIS OF Β-SUBSTITUTED α-AMINO ACIDS VIA A CHIRAL Ni(II) COMPLEX OF DEHYDROALANINE
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An efficient approach to the asymmetric synthesis of β-substituted (S)-alanines is describen.The chiral Ni(II) complex of a Schiff base derived from (S)-o-N-(N-benzylpropyl)aminobenzophenone (BBP) and glycine was treated with formaldehyde and sodium methoxide to give a corresponding (R)-serine complex which, in turn, was converted to the chiral Ni(II) dehydroalanine complex.Michael type base catalyzed addition of nucleophiles (including MeOH, Me2NH, PhCH2NH2, imidazole, PhSH, PhCH2SH,, malonic ester and benzylmagnesium chloride) produced a mixture of diastereoisomeric complexes with a 70-90percent excess of S,S (or L,L) isomers over the S,R (or L,D) ones.The cleavage of pure diastereoisomers with aqueous HCl gave, in good yields, β-substituted (S) (or L)-alanines and regenerated the chiral auxiliary (BBP).
- Belokon, , Yuri N.,Sagyan, Ashot S.,Djamgaryan, Silva M.,Bakhmutov, Vladimir I.,Belikov, Vasili M.
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p. 5507 - 5514
(2007/10/02)
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