Enzymatic synthesis of β-lactam acids (review)

Sklyarenko, A. V.; Eldarov, M. A.; Kurochkina, V. B.; Yarotsky, S. V.

doi:10.1134/s0003683815060150

Cited by 17 publications

(5 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glycoside hydrolases (Adlercreutz, 2017;Seibel et al, 2006;Vera et al, 2020;Zeuner, Jers, Mikkelsen, & Meyer, 2014), lipases (Adlercreutz, 2017;Subileau et al, 2017), amidases (Bruggink, Roos, & de Vroom, 1998;Giordano et al, 2006;Gololobov et al, 1990;Sio & Quax, 2004;Sklyarenko, El'darov, Kurochkina, & Yarotsky, 2015), and phosphatases (Ishikawa et al, 2002;Tasnádi, Staśko, Ditrich, Hall, & Faber, 2020; are industrial enzymes used in these synthetic processes. Mechanistically, the enzymatic reactions proceed in two catalytic steps via a covalent enzyme intermediate (Gololobov, Borisov, Belikov, & Švedas, 1988;Kasche, 1986;Marsden et al, 2020;Seibel et al, 2006;Zeuner et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

On the donor substrate dependence of group‐transfer reactions by hydrolytic enzymes: Insight from kinetic analysis of sucrose phosphorylase‐catalyzed transglycosylation

Klimacek

Sigg

Nidetzky

2020

Biotech & Bioengineering

View full text Add to dashboard Cite

Chemical group‐transfer reactions by hydrolytic enzymes have considerable importance in biocatalytic synthesis and are exploited broadly in commercial‐scale chemical production. Mechanistically, these reactions have in common the involvement of a covalent enzyme intermediate which is formed upon enzyme reaction with the donor substrate and is subsequently intercepted by a suitable acceptor. Here, we studied the glycosylation of glycerol from sucrose by sucrose phosphorylase (SucP) to clarify a peculiar, yet generally important characteristic of this reaction: partitioning between glycosylation of glycerol and hydrolysis depends on the type and the concentration of the donor substrate used (here: sucrose, α‐d‐glucose 1‐phosphate (G1P)). We develop a kinetic framework to analyze the effect and provide evidence that, when G1P is used as donor substrate, hydrolysis occurs not only from the β‐glucosyl‐enzyme intermediate (E‐Glc), but additionally from a noncovalent complex of E‐Glc and substrate which unlike E‐Glc is unreactive to glycerol. Depending on the relative rates of hydrolysis of free and substrate‐bound E‐Glc, inhibition (Leuconostoc mesenteroides SucP) or apparent activation (Bifidobacterium adolescentis SucP) is observed at high donor substrate concentration. At a G1P concentration that excludes the substrate‐bound E‐Glc, the transfer/hydrolysis ratio changes to a value consistent with reaction exclusively through E‐Glc, independent of the donor substrate used. Collectively, these results give explanation for a kinetic behavior of SucP not previously accounted for, provide essential basis for design and optimization of the synthetic reaction, and establish a theoretical framework for the analysis of kinetically analogous group‐transfer reactions by hydrolytic enzymes.

show abstract

Section: Introductionmentioning

confidence: 99%

On the donor substrate dependence of group‐transfer reactions by hydrolytic enzymes: Insight from kinetic analysis of sucrose phosphorylase‐catalyzed transglycosylation

Klimacek

Sigg

Nidetzky

2020

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…Over the past three decades, the chemical technology involved in producing antibiotics of the β-lactam class has progressively been replaced by biocatalyst technology which is cheaper and tends to be safer because of minimal side effects (A. . This shift is attributed to several factors contributing to the significant growth and development of biocatalysts are related to (1) the high quality of the final product; (2) the undeniable ecological benefits of biocatalysts such as mild reaction conditions (pH, temperature), excluding toxic reagents and providing increased product/waste ratios (decreased organic solvents and reagents); (3) increase in economic efficiency and competitiveness of enzymatic technology due to the improvement of each aspect (strain, biocatalyst, enzymatic transformation), as well as due to optimal process integration in the application of the one pot process (Alemzadeh et al, 2010;Sklyarenko et al, 2015). The current focus in the production of β-lactam antibiotics includes the synthesis of ampicillin, amoxicillin, cephalexin, cefachlor, and cefazolin.…”

Section: Role Of Pga Enzyme In Antibiotic Productionmentioning

confidence: 99%

“…Synthesis under kinetic control (KCS) involves a complex strategy. Conditions in KCS for β-lactam antibiotic synthesis have been optimized across various parameters such as pH (Sawant et al, 2020b), ionic strength (D. Yang et al, 2016), temperature (Sklyarenko et al, 2015), molar ratio of acyl donors and nucleophiles (Dai et al, 2001;Deng et al, 2015), and the composition of the medium with organic cosolvent (Deng et al, 2016), all aimed at enhancing the synthesis/hydrolysis ratio (S/H). This optimization has shown success in the synthesis of cephalologlysin in methanol, as well as ampicillin and cephalexin in glycol (Zhu & Cao, 2014).…”

Section: Role Of Pga Enzyme In Antibiotic Productionmentioning

confidence: 99%

Manipulation Strategy to Increase Expression Level of Soluble Recombinant Protein Penicillin G Acylase (PGA) in Bacterial Host Escherichia coli: A Review Article

Amin,

Sismindari,

Aniqah

et al. 2024

Indonesian J Pharm

View full text Add to dashboard Cite

The strategy of producing PGA on a massive scale with high levels of soluble protein can be through recombinant genetic techniques and expressed in a certain host. E. coli is still a popular bacterial host to produce a recombinant protein which has advantages such as fast growth, low production cost, and high expression rate. Apart from its advantages, E. coli as a production host also has disadvantages including the expression of recombinant proteins often failing to form the proper folding conformation which makes the protein biologically inactive. Many strategies can be developed to overcome these problems, such as the selection of the host strain (E. coli HB101 & JM109), fusion protein to enhance the recovery of soluble protein (MBP & NusA), optimization of fermentation (low-temperature incubation), and optimization of the protein isolation process for the recovery of active PGA (Freeze-thawing method).

show abstract

“…Numerous enzymes successfully catalyzed the transformation of some compounds into pharmacological species, this category including antibiotics [136], analgesics [137], and some anti-inflammatory drugs [138]. An example is presented by Gilani and collaborators, who studied the production of (S)-naproxen under the action of three biocatalysts: CHI/lipase composite microparticles, CHI/lipase microparticles cross-linked with GA, and microparticles obtained by lipase immobilization in a commercial resin of Amberlite XAD7 type [138].…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Polymer/Enzyme Composite Materials—Versatile Catalysts with Multiple Applications

Petrila¹,

Gradinaru

Bucătariu³

et al. 2022

Chemistry

View full text Add to dashboard Cite

A significant interest was granted lately to enzymes, which are versatile catalysts characterized by natural origin, with high specificity and selectivity for particular substrates. Additionally, some enzymes are involved in the production of high-valuable products, such as antibiotics, while others are known for their ability to transform emerging contaminates, such as dyes and pesticides, to simpler molecules with a lower environmental impact. Nevertheless, the use of enzymes in industrial applications is limited by their reduced stability in extreme conditions and by their difficult recovery and reusability. Rationally, enzyme immobilization on organic or inorganic matrices proved to be one of the most successful innovative approaches to increase the stability of enzymatic catalysts. By the immobilization of enzymes on support materials, composite biocatalysts are obtained that pose an improved stability, preserving the enzymatic activity and some of the support material’s properties. Of high interest are the polymer/enzyme composites, which are obtained by the chemical or physical attachment of enzymes on polymer matrices. This review highlights some of the latest findings in the field of polymer/enzyme composites, classified according to the morphology of the resulting materials, following their most important applications.

show abstract

Enzymatic synthesis of β-lactam acids (review)

Cited by 17 publications

References 56 publications

On the donor substrate dependence of group‐transfer reactions by hydrolytic enzymes: Insight from kinetic analysis of sucrose phosphorylase‐catalyzed transglycosylation

On the donor substrate dependence of group‐transfer reactions by hydrolytic enzymes: Insight from kinetic analysis of sucrose phosphorylase‐catalyzed transglycosylation

Manipulation Strategy to Increase Expression Level of Soluble Recombinant Protein Penicillin G Acylase (PGA) in Bacterial Host Escherichia coli: A Review Article

Polymer/Enzyme Composite Materials—Versatile Catalysts with Multiple Applications

Contact Info

Product

Resources

About