Enzymatic approach to both enantiomers of N-Boc hydrophobic amino acids

Agosta, Eleonora; Caligiuri, Antonio; D’Arrigo, Paola; Servi, Stefano De; Tessaro, Davide; Canevotti, Renato

doi:10.1016/j.tetasy.2006.07.012

Cited by 23 publications

(14 citation statements)

References 47 publications

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“…L‐tert leucine (L‐tle) has been widely used as a chiral building block in many asymmetric reactions for the synthesis of anti‐tumor and anti‐HIV drugs . The enzymatic catalysis of L‐tle have been developed in past decades and several biocatalysts were found to be capable of producing L‐tle including leucine dehydrogenase , branched chain aminotransferase , penicillin acylases , lipase , amidase , protease . Among the above‐listed reports, leucine dehydrogenase (LeuDH, EC 1.4.1.9) and formate dehydrogenase (FDH, EC 1.2.1.2) based cofactor regeneration system was regarded as a desirable process with high catalytic and economic efficiency .…”

Section: Introductionmentioning

confidence: 99%

Engineering bi‐functional enzyme complex of formate dehydrogenase and leucine dehydrogenase by peptide linker mediated fusion for accelerating cofactor regeneration

Zhang

Wang

et al. 2017

Engineering in Life Sciences

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This study reports the application of peptide linker in the construction of bi‐functional formate dehydrogenase (FDH) and leucine dehydrogenase (LeuDH) enzymatic complex for efficient cofactor regeneration and L‐tert leucine (L‐tle) biotransformation. Seven FDH‐LeuDH fusion enzymes with different peptide linker were successfully developed and displayed both parental enzyme activities. The incorporation order of FDH and LeuDH was investigated by predicting three‐dimensional structures of LeuDH‐FDH and FDH‐LeuDH models using the I‐TASSER server. The enzymatic characterization showed that insertion of rigid peptide linker obtained better activity and thermal stability in comparison with flexible peptide linker. The production rate of fusion enzymatic complex with suitable flexible peptide linker was increased by 1.2 times compared with free enzyme mixture. Moreover, structural analysis of FDH and LeuDH suggested the secondary structure of the N‐, C‐terminal domain and their relative positions to functional domains was also greatly relevant to the catalytic properties of the fusion enzymatic complex. The results show that rigid peptide linker could ensure the independent folding of moieties and stabilized enzyme structure, while the flexible peptide linker was likely to bring enzyme moieties in close proximity for superior cofactor channeling.

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Section: Introductionmentioning

confidence: 99%

Engineering bi‐functional enzyme complex of formate dehydrogenase and leucine dehydrogenase by peptide linker mediated fusion for accelerating cofactor regeneration

Zhang

Wang

et al. 2017

Engineering in Life Sciences

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“…To study the effect of pH on fusion enzyme and free enzymes, enzyme activities were measured in buffers with different pH (0.2 M potassium phosphate buffer including NH4+, pH 6-8; 0.2 M NH4Cl-NH3•H2O buffer, pH [8][9][10][11]. The effect of temperature on fusion enzyme and free enzymes were tested over the temperature range of 30-90°C.…”

Section: Enzyme Characterizationmentioning

confidence: 99%

“…However, the disadvantages were signi cant and pervasive existed in most chiral l-tert chemical catalysis producing process, including energy-consuming, environmentally-unfriendly, and low conversion and enantioselectivity [3,4]. The greener biocatalysts, such as leucine dehydrogenase [5], branched chain aminotransferase [6], amidases [7], and proteases [8], penicillinyl enzymes [9], lipases [10], have been developed and applied in L-tle enzymatically producing process over the past few decades. Among those biocatalysts, leucine dehydrogenase (LeuDH, EC 1.4.1.9) exhibited an outstanding conversion e ciency and enantioselectivity which became the main method of L-tle synthesis in the market [11].…”

Section: Introductionmentioning

confidence: 99%

Construction and Characterization of a Novel Glucose Dehydrogenase-Leucine Dehydrogenase Bifunctional Enzyme for the Biosynthesis of L-Tert-Leucine

Liao

Zhang

Wang

et al. 2020

Preprint

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Background: Biosynthesis of L-tert-leucine (L-tle), a significant pharmaceutical intermediate, by a cofactor regeneration system friendly and efficiently is a worthful goal all the time. The cofactor regeneration system of leucine dehydrogenase (LeuDH) and glucose dehydrogenase (GDH) has showed great coupling catalytic efficiency in the synthesis of L-tle, however the multi-enzyme complex of GDH and LeuDH has never been constructed successfully.Results: In this work, a novel bifunctional enzyme (GDH-R3-LeuDH) for the efficient biosynthesis of L-tle was constructed by the fusion of LeuDH and GDH mediated with a rigid peptide linker. Compared with the free enzymes, both the environmental tolerance and thermal stability of GDH-R3-LeuDH had a great improved since the fusion structure. The fusion structure also accelerated the cofactor regeneration rate and maintained the enzyme activity, so the productivity and yeild of L-tle by GDH-R3-LeuDH was all enhanced by 2-fold. Finally, the space-time yield of L-tle catalyzing by GDH-R3-LeuDH whole cells could achieve 2136 g/L/d in a 200 mL scale system under the optimal catalysis conditions (pH 9.0, 30℃, 0.4 mM of NAD+ and 500 mM of a substrate including trimethylpyruvic acid and glucose). Conclusions: It is the first report about the fusion of GDH and LeuDH as the multi-enzyme complex to synthesize L-tle and reach the highest space-time yield up to now. These results demonstrated the great potential of the GDH-R3-LeuDH bifunctional enzyme for the efficient biosynthesis of L-tle.

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“…Other applications of Asu in peptide engineering and as a building block are of notable importance [ 5 – 6 ]. For this, and other reasons, several synthetic routes to Asu have been developed [ 7 – 9 ] which often uses chemical or enzymatic resolution of a racemate [ 10 ]. However, the chemical synthesis of an orthogonally protected Asu derivative from easily available sources [ 11 ] for potential applications remains important.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

Chattopadhyay

Sil

Mukherjee

2017

Beilstein J. Org. Chem.

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A new synthesis of the important amino acid 2-aminosuberic acid from aspartic acid is reported. The methodology involves the alternate preparation of (S)-2-aminohept-6-enoate ester as a building block and its diversification through a cross-metathesis reaction to prepare the title compounds. The utility of the protocol is demonstrated through the preparation of three suberic acid derivatives of relevance to the design and the synthesis of peptides of biological relevance.

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Enzymatic approach to both enantiomers of N-Boc hydrophobic amino acids

Cited by 23 publications

References 47 publications

Engineering bi‐functional enzyme complex of formate dehydrogenase and leucine dehydrogenase by peptide linker mediated fusion for accelerating cofactor regeneration

Engineering bi‐functional enzyme complex of formate dehydrogenase and leucine dehydrogenase by peptide linker mediated fusion for accelerating cofactor regeneration

Construction and Characterization of a Novel Glucose Dehydrogenase-Leucine Dehydrogenase Bifunctional Enzyme for the Biosynthesis of L-Tert-Leucine

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

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