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Article Abstract

6-Aminopenicillanic acid (6-APA) is used for synthesis of semisynthetic antibiotics. Polymer-salt aqueous two-phase systems (ATPSs) were applied for separation of 6-APA and phenyl acetic acid (PAA), as the products of hydrolyzation reaction of Penicillin G/Penicillin V. The binodal curves of ATPS composed of a copolymer (reverse Pluronic 10R5, Pluronic L35 and PEG-ran-PPG) and a salt (Tri-sodium citrate, tri-potassium citrate, di-potassium phosphate, sodium sulphate and magnesium sulphate) were obtained. The results show that, at a fixed PPG/PEG ratio, block copolymers have larger two-phase region compared with random copolymer. After screening on the partition coefficient of PAA and 6-APA separately, NaSO was selected for studying the effect of the copolymer structure and the composition of salt and copolymer on partitioning, considering higher selectivity of PAA and 6-APA. 10R5-NaSO ATPS was selected as the most appropriate system for separation of 6-APA and PAA. This system was used for separation of mixture of 6-APA and PAA. The results show that selectivity was [Formula: see text] 53 and smaller in a system, containing a mixture of 6-APA and PAA. This observation can be justified by the interaction between 6-APA and PAA. Molecular interaction between these two molecules were investigated by the Flory-Huggins interaction parameter.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875977PMC
http://dx.doi.org/10.1038/s41598-021-82476-xDOI Listing

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6-Aminopenicillanic acid (6-APA) is used for synthesis of semisynthetic antibiotics. Polymer-salt aqueous two-phase systems (ATPSs) were applied for separation of 6-APA and phenyl acetic acid (PAA), as the products of hydrolyzation reaction of Penicillin G/Penicillin V. The binodal curves of ATPS composed of a copolymer (reverse Pluronic 10R5, Pluronic L35 and PEG-ran-PPG) and a salt (Tri-sodium citrate, tri-potassium citrate, di-potassium phosphate, sodium sulphate and magnesium sulphate) were obtained.

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Penicillin G acylase (PGA) is a commercially important enzyme that cleaves penicillin G to 6-amino penicillanic acid (6-APA) and phenyl acetic acid (PAA). The strain Bacillus badius has been identified as potential producer of PGA. A detailed calorimetric investigation on PGA production was carried out to enable generation of thermokinetic data possible for commercial application.

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In light of unrestricted use of first-generation penicillins, these antibiotics are now superseded by their semisynthetic counterparts for augmented antibiosis. Traditional penicillin chemistry involves the use of hazardous chemicals and harsh reaction conditions for the production of semisynthetic derivatives and, therefore, is being displaced by the biosynthetic platform using enzymatic transformations. Penicillin G acylase (PGA) is one of the most relevant and widely used biocatalysts for the industrial production of β-lactam semisynthetic antibiotics.

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Enzymatic hydrolysis of penicillin for 6-APA production in three-liquid-phase system.

Appl Biochem Biotechnol

February 2008

Laboratory of Separation Science and Engineering, Institute of Process Engineering, Chinese Academy of Science, Beijing 100080, China.

A dodecane/thermosensitive polymer/water three-liquid-phase system was introduced for enzymatic hydrolysis of penicillin G (Pen G) for 6-aminopenicillanic acid (6-APA). The enzyme was covalently attached to the terminal of PEO-PPO-PEO polymer (L63), which would be transferred into a polymer coacervate phase at high temperature above its "cloud point". 6-APA was primarily resided in the aqueous phase due to its zwitterionic nature.

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A rapid, sensitive and selective ion-pair reversed-phase liquid chromatography-electrospray ionization isotope dilution tandem mass spectrometry (IP-LC-ESI-ID-MS/MS) was developed for quantitative analysis of free intracellular metabolites in cell cultures. As an application a group of compounds involved in penicillin biosynthesis pathway of Penicillium chrysogenum cells, such as penicillin G (PenG), 6-aminopenicillanic acid (6-APA), benzylpenicilloic acid (PIO), ortho-hydroxyphenyl acetic acid (o-OH-PAA), phenylacetic acid (PAA), 6-oxopipeidine-2-carboxylic acid (OPC), 8-hydroxypenicillic acid (8-HPA), L-alpha-(delta-aminoadipyl)-L-alpha-cystenyl-D-alpha-valine (ACV) and isopenicillin N (IPN) were chosen. (13)C-labeled analogs of the metabolites were added to the sample solutions as internal standards (I.

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