Unnatural amino acids: production and biotechnological potential

Narancic, Tanja; Almahboub, Sarah A; O’Connor, Kevin E.

doi:10.1007/s11274-019-2642-9

Cited by 86 publications

(73 citation statements)

References 98 publications

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“…The wide array of available NPAAs can be introduced in the peptide therapeutics to increase stability, potency, and permeability, which can lead to improved oral bioavailability utilizes various enzymatic reactions to produce enantiomeric NPAAs with a higher yield, it requires fewer steps compared to chemical synthesis, and often can be done in the aqueous media. The major limiting factor for this method is the high cost of the cofactors when large-scale production is required (Narancic et al 2019). Overall, artificial NPAAs including D enantiomer, PTM, and analogous amino acids serve as versatile tools in various scientific disciplines, including drug discovery, study of protein structure, protein trafficking, and protein optimization (Narancic et al 2019).…”

Section: Naturally Occurring and Synthetic Npaasmentioning

confidence: 99%

Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics

et al. 2020

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With the development of modern chemistry and biology, non-proteinogenic amino acids (NPAAs) have become a powerful tool for developing peptide-based drug candidates. Drug-like properties of peptidic medicines, due to the smaller size and simpler structure compared to large proteins, can be changed fundamentally by introducing NPAAs in its sequence. While peptides composed of natural amino acids can be used as drug candidates, the majority have shown to be less stable in biological conditions. The impact of NPAA incorporation can be extremely beneficial in improving the stability, potency, permeability, and bioavailability of peptide-based therapies. Conversely, undesired effects such as toxicity or immunogenicity should also be considered. The impact of NPAAs in the development of peptide-based therapeutics is reviewed in this article. Further, numerous examples of peptides containing NPAAs are presented to highlight the ongoing development in peptide-based therapeutics.

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Section: Naturally Occurring and Synthetic Npaasmentioning

confidence: 99%

Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics

et al. 2020

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“…Biocatalytic synthesis offers the benefits of mild reaction conditions, fewer synthetic steps, great stereo‐ and enantioselectivity, and no need for removing protective groups or disposing of toxic waste materials . Although both in vitro and in vivo biocatalytic methodologies for the synthesis of ncAAs have been reported, in vivo approaches are easily scalable, eliminate the need for final product purification, and can be combined in situ with genetic‐code expansion. Therefore, we will focus on in vivo biocatalytic approaches in microbial hosts, such as E .…”

Section: Intracellular Synthesis Of Ncaas In Bacterial Hostsmentioning

confidence: 99%

Tackling Achilles’ Heel in Synthetic Biology: Pairing Intracellular Synthesis of Noncanonical Amino Acids with Genetic‐Code Expansion to Foster Biotechnological Applications

Biava

2020

ChemBioChem

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For the last two decades, synthetic biologists have been able to unlock and expand the genetic code, generating proteins with unique properties through the incorporation of noncanonical amino acids (ncAAs). These evolved biomaterials have shown great potential for applications in industrial biocatalysis, therapeutics, bioremediation, bioconjugation, and other areas. Our ability to continue developing such technologies depends on having relatively easy access to ncAAs. However, the synthesis of enantiomerically pure ncAAs in practical quantitates for large‐scale processes remains a challenge. Biocatalytic ncAA production has emerged as an excellent alternative to traditional organic synthesis in terms of cost, enantioselectivity, and sustainability. Moreover, biocatalytic synthesis offers the opportunity of coupling the intracellular generation of ncAAs with genetic‐code expansion to overcome the limitations of an external supply of amino acid. In this minireview, we examine some of the most relevant achievements of this approach and its implications for improving technological applications derived from synthetic biology.

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“…Enantiopure NcAAs are of considerable economic importance because of their broad industrial applications (Patel, 2013;Narancic et al, 2019). The global AA market increased from 0.7 million tons in 1985 to 9.3 Million Tons in 2019, and is expected to reach a volume of 11.9 million tons in 2025 (Ikeda and Takeno, 2013;IMARC group, 2019).…”

Section: Biomedical and Biotechnological Applications Of Ncaasmentioning

confidence: 99%

“…The occurrence and biological activity of NcAAs in vivo is hugely diverse, and some of their properties have been reflected in different papers (Wagner and Musso, 1983;Hunt, 1985;Nunn et al, 2010;Yamane et al, 2010;Walsh et al, 2013;Blaskovich, 2016;Zou et al, 2018;Narancic et al, 2019;Hedges and Ryan, 2020). Broadly, several NcAAs are utilized as intermediates in primary metabolic pathways (e.g., homoserine, ornithine, citrulline,.…”

Section: Introductionmentioning

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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Unnatural amino acids: production and biotechnological potential

Cited by 86 publications

References 98 publications

Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics

Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics

Tackling Achilles’ Heel in Synthetic Biology: Pairing Intracellular Synthesis of Noncanonical Amino Acids with Genetic‐Code Expansion to Foster Biotechnological Applications

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

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