Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

Özdemir, Özlem; Gürkan, Perihan; Özçelık, Berrın; Oyardı, Özlem

doi:10.1016/j.molstruc.2015.10.074

Cited by 17 publications

(2 citation statements)

References 35 publications

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“…To achieve this, at the first stage, penicillin nucleus or 6aminopenicillanic acid (6-APA) is obtained from PenG as a result of the deacylation reaction in vitro by amidase enzymes of bacterial origin (penicillin G amidase, EC 3.5.1.11) [56,185]. Then, various semisynthetic penicillins are obtained by grafting different side chains onto 6-APA [186][187][188] (Figure 6a).…”

Section: Fermentation Of P Chrysogenum For Penicillin G (Peng) Produc...mentioning

confidence: 99%

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Zhgun

2023

Fermentation

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The natural fermentation of antibiotics, along with semi-synthetic and synthetic approaches, is one of the most important methods for their production. The majority of the antibiotic market comes from the fermentation of high-yielding (HY) fungal strains. These strains have been obtained since the 1950s from wild-type (WT) isolates as a result of classical strain improvement (CSI) programs primarily involving multi-round random mutagenesis and screening. However, the molecular basis leading to high-yield production was unknown. In recent years, due to the application of multiomic approaches, key changes that occur in CSI programs, with WT strains that become HY industrial producers of a particular antibiotic, have begun to be understood. It becomes obvious that, during CSI, certain universal events are selected, which lead both to a direct increase in the production of the target metabolite and affect other vital processes of the cell (side mutations). These key events include: the upregulation of the target biosynthetic gene cluster (BGC), changes in the system of global regulation, disruption of alternative BGCs, the rearrangement of energy fluxes in favor of the target SM (secondary metabolite), changes in the regulation of the response to stress, and the redirection of primary metabolic pathways to obtain more precursors for target production. This knowledge opens up the possibility of both introducing targeted changes using genetic engineering methods when creating new producers and increasing the production of CSI strains as a result of fermentation with low-molecular compounds, targeted to compensate for the effects of side mutations.

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Section: Fermentation Of P Chrysogenum For Penicillin G (Peng) Produc...mentioning

confidence: 99%

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Zhgun

2023

Fermentation

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“…The modifications provided chemically stable molecules with reduced side effects. Resistance to semi-synthetic antibacterial has also evolved rapidly [11]. Semi-synthetic antibiotics with chemical modification saw the dawn of the medicinal chemistry era, which, along with the Waksman platform, yielded clinically relevant antibiotics with significant potency and lesser side effects.…”

Section: The Drug Portfoliomentioning

confidence: 99%

Alternate Antimicrobial Therapies and Their Companion Tests

et al. 2023

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New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with the emergence of resistance, resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies with clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers, and phages. Clinical diagnostics optimize the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic-based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious diseases include detection, monitoring of response, and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy, this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives with the use of alternate therapeutics, with a particular focus on companion diagnostic applications in infectious diseases.

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Optimization of penicillin G acylase immobilized on glutaraldehyde‐modified titanium dioxide

Chen

Liu

et al. 2019

Biotech and App Biochem

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In this work, TiO2, which was modified by glutaraldehyde, was adopted as the carrier; the penicillin G acylase (PGA) was immobilized and the influence of immobilized conditions, such as pH of solution, the concentration of PGA, the immobilization temperature, and the reaction time, on the catalytic performance of the immobilized PGA was investigated and optimized. During this process, potassium penicillin G (PG) was chosen as substrate, and the quantity of 6‐aminopenicillanic acid (6‐APA) produced by PG at the temperature of 25 °C for 3 Min in neutral solution was conscripted as the evaluation foundation, indexes, containing the loading capacity (ELC), the activity (EA), and activity retention rate (EAR), were calculated based on quantities of produced 6‐APA and compared with finding out the suitable conditions. Results showed that when the solution pH, PGA concentration, immobilization temperature, and reaction time were 8.0, 2.5% (v/v), 35 °C, and 24 H, respectively, ELC, EA, and EAR presented optimal values of 9,190 U, 14,969 U/g, and 88.5% relatedly. After that, the stability and reusability of immobilized PGA were studied, and the results documented that the pH resistance, thermal stability, and storage stability of immobilized PGA were significantly improved. This work provided technique support for the practical application of immobilized PGA carrier.

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Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

Cited by 17 publications

References 35 publications

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Alternate Antimicrobial Therapies and Their Companion Tests

Optimization of penicillin G acylase immobilized on glutaraldehyde‐modified titanium dioxide

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