Stereoselective synthesis of L‐[<sup>15</sup>N] amino acids with glucose dehydrogenase and galactose mutarotase as NADH regenerating system

Chiriac, Maria; Lupan, Iulia; Bucurenci, Nadia; Popescu, Octavian; Palibroda, Nicolae

doi:10.1002/jlcr.1496

Cited by 9 publications

(2 citation statements)

References 14 publications

(16 reference statements)

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“…Apart from this study, few other works have described the synthesis of l ‐norvaline by using biocatalytic systems such as leucine dehydrogenase coupled with a glucose dehydrogenase as a cofactor regenerating enzyme and a trienzymatic system coupling leucine dehydrogenase, glucose dehydrogenase and galactomutarotase . However, these systems use either soluble enzymes or whole cells, which hampers their reuse for sequential operational cycles and their integration into packed reactors for continuous operation.…”

Section: Resultsmentioning

confidence: 99%

Sustainable and Continuous Synthesis of Enantiopure l‐Amino Acids by Using a Versatile Immobilised Multienzyme System

et al. 2017

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The enzymatic synthesis of α-amino acids is a sustainable and efficient alternative to chemical processes, through which achieving enantiopure products is difficult. To more address this synthesis efficiently, a hierarchical architecture that irreversibly co-immobilises an amino acid dehydrogenase with polyethyleneimine on porous agarose beads has been designed and fabricated. The cationic polymer acts as an irreversible anchoring layer for the formate dehydrogenase. In this architecture, the two enzymes and polymer colocalise across the whole microstructure of the porous carrier. This multifunctional heterogeneous biocatalyst was kinetically characterised and applied to the enantioselective synthesis of a variety of canonical and noncanonical α-amino acids in both discontinuous (batch) and continuous modes. The co-immobilised bienzymatic system conserves more than 50 % of its initial effectiveness after five batch cycles and 8 days of continuous operation. Additionally, the environmental impact of this process has been semiquantitatively calculated and compared with the state of the art.

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Section: Resultsmentioning

confidence: 99%

Sustainable and Continuous Synthesis of Enantiopure l‐Amino Acids by Using a Versatile Immobilised Multienzyme System

et al. 2017

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“…In an analogous process, Bristol-Myers Squibb produced 197 kg of L -allysine ethylene acetal using a 1600 L reactor, with dried cells containing PheDH together FDH ( Liese et al, 2006 ). 15 N-labeled norvaline and norleucine were produced combining LeuDH with a GDH/galactose mutarotase as cofactor recycling system to increase its effectivity (80–95% yield; Chiriac et al, 2008 ). On the other hand, different D -α-AAs have been obtained by AADH-based MECs (including 13 C- and/or 15 N-labeled DAAs; Vedha-Peters et al, 2006 ; Akita et al, 2018 ).…”

Section: Multienzymatic Cascades For the Production Of Ncaasmentioning

confidence: 99%

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Martínez‐Rodríguez

Torres

Sánchez

et al. 2020

Front. Bioeng. Biotechnol.

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The 22 genetically encoded amino acids (AAs) present in proteins (the 20 standard AAs together with selenocysteine and pyrrolysine), are commonly referred as proteinogenic AAs in the literature due to their appearance in ribosome-synthetized polypeptides. Beyond the borders of this key set of compounds, the rest of AAs are generally named imprecisely as non-proteinogenic AAs, even when they can also appear in polypeptide chains as a result of post-transductional machinery. Besides their importance as metabolites in life, many of D-α-and L-α-"non-canonical" amino acids (NcAAs) are of interest in the biotechnological and biomedical fields. They have found numerous applications in the discovery of new medicines and antibiotics, drug synthesis, cosmetic, and nutritional compounds, or in the improvement of protein and peptide pharmaceuticals. In addition to the numerous studies dealing with the asymmetric synthesis of NcAAs, many different enzymatic pathways have been reported in the literature allowing for the biosynthesis of NcAAs. Due to the huge heterogeneity of this group of molecules, this review is devoted to provide an overview on different established multienzymatic cascades for the production of non-canonical D-α-and L-α-AAs, supplying neophyte and experienced professionals in this field with different illustrative examples in the literature. Whereas the discovery of new or newly designed enzymes is of great interest, dusting off previous enzymatic methodologies by a "back and to the future" strategy might accelerate the implementation of new or improved multienzymatic cascades.

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Efficient synthesis of d-branched-chain amino acids and their labeled compounds with stable isotopes using d-amino acid dehydrogenase

Akita

Suzuki

Doi

et al. 2013

Appl Microbiol Biotechnol

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D-Branched-chain amino acids (D-BCAAs) such as D-leucine, D-isoleucine, and D-valine are known to be peptide antibiotic intermediates and to exhibit a variety of bioactivities. Consequently, much effort is going into achieving simple stereospecific synthesis of D-BCAAs, especially analogs labeled with stable isotopes. Up to now, however, no effective method has been reported. Here, we report the establishment of an efficient system for enantioselective synthesis of D-BCAAs and production of D-BCAAs labeled with stable isotopes. This system is based on two thermostable enzymes: D-amino acid dehydrogenase, catalyzing NADPH-dependent enantioselective amination of 2-oxo acids to produce the corresponding D-amino acids, and glucose dehydrogenase, catalyzing NADPH regeneration from NADP(+) and D-glucose. After incubation with the enzymes for 2 h at 65°C and pH 10.5, 2-oxo-4-methylvaleric acid was converted to D-leucine with an excellent yield (>99 %) and optical purity (>99 %). Using this system, we produced five different D-BCAAs labeled with stable isotopes: D-[1-(13)C,(15)N]leucine, D-[1-(13)C]leucine, D-[(15)N]leucine, D-[(15)N]isoleucine, and D-[(15)N]valine. The structure of each labeled D-amino acid was confirmed using time-of-flight mass spectrometry and nuclear magnetic resonance analysis. These analyses confirmed that the developed system was highly useful for production of D-BCAAs labeled with stable isotopes, making this the first reported enzymatic production of D-BCAAs labeled with stable isotopes. Our findings facilitate tracer studies investigating D-BCAAs and their derivatives.

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Stereoselective synthesis of L‐[¹⁵N] amino acids with glucose dehydrogenase and galactose mutarotase as NADH regenerating system

Cited by 9 publications

References 14 publications

Sustainable and Continuous Synthesis of Enantiopure l‐Amino Acids by Using a Versatile Immobilised Multienzyme System

Sustainable and Continuous Synthesis of Enantiopure l‐Amino Acids by Using a Versatile Immobilised Multienzyme System

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Efficient synthesis of d-branched-chain amino acids and their labeled compounds with stable isotopes using d-amino acid dehydrogenase

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Stereoselective synthesis of L‐[15N] amino acids with glucose dehydrogenase and galactose mutarotase as NADH regenerating system

Cited by 9 publications

References 14 publications

Sustainable and Continuous Synthesis of Enantiopure l‐Amino Acids by Using a Versatile Immobilised Multienzyme System

Sustainable and Continuous Synthesis of Enantiopure l‐Amino Acids by Using a Versatile Immobilised Multienzyme System

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Efficient synthesis of d-branched-chain amino acids and their labeled compounds with stable isotopes using d-amino acid dehydrogenase

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Stereoselective synthesis of L‐[¹⁵N] amino acids with glucose dehydrogenase and galactose mutarotase as NADH regenerating system