Extraction of clavulanic acid using aqueous two‐phase micellar system

Andrade, Evelyn Guedes de; Silva, Marcela de Siqueira Cardoso; Haga, Raquel Brandão; Santos, Victor José Correia; Pessoa, Adalberto; Rangel-Yagui, Carlota de Oliveira

doi:10.1002/bab.20

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…The Na 2 SO 4 containing systems showed an interesting CA partition coefficient (K CA = 9.15 ± 1.06). This value was higher than the one observed in an earlier study [4,38] of CA purification using two different aqueous two-phase micellar systems composed by the surfactants n-decyltetraethylene oxide and dodecylmethylamine oxide, and surfactant Triton X-114 and the anionic one AOT, where the highest values of K CA were 0.94 and 1.48, respectively. A high partition coefficient (K CA = 8.2) was obtained in a previous CA fermentative extraction study [39] using PEG and phosphate salts.…”

Section: Partition Studies With Pure Ca Pure and In The Fermented Brothcontrasting

confidence: 68%

A stable liquid–liquid extraction system for clavulanic acid using polymer-based aqueous two-phase systems

Pereira

Santos

Johansson

et al. 2012

Separation and Purification Technology

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a b s t r a c tThe partitioning of Clavulanic Acid (CA) in a novel inexpensive and stable aqueous two-phase system (ATPS) composed by poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) has been studied. The aqueous two-phase systems are formed by mixing both polymers with a salt (NaCl or Na 2 SO 4 ) and an aqueous solution of CA. The stability of CA on the presence of both polymers was investigated and it was observed that these polymers do not degrade the biomolecule. The effect of PEG-molecular size, polymer concentrations on the commercial CA partitioning has been studied, at 25°C. The data showed that commercial CA was preferentially partitioned for the PEG-rich phase with a partition coefficient (K CA ) between 1 and 12 in the PEG/NaPA aqueous two phase systems supplemented with NaCl and Na 2 SO 4 . The partition to the PEG phase was increased in the systems with high polymer concentrations. Furthermore, Na 2 SO 4 caused higher CA preference for the PEG-phase than NaCl. The systems having a composition with 10 wt.% of PEG4000, 20 wt.% of NaPA8000 and 6 wt.% of Na 2 SO 4 were selected as the optimal ones in terms of recovery of CA from fermented broth of Streptomyces clavuligerus. The partitioning results (K CA = 9.15 ± 1.06) are competitive with commercial extraction methods of CA (K CA = 11.91 ± 2.08) which emphasizes that the system PEG/NaPA/Na 2 SO 4 can be used as a new process to CA purification/concentration from fermented broth.

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Section: Partition Studies With Pure Ca Pure and In The Fermented Brothcontrasting

confidence: 68%

A stable liquid–liquid extraction system for clavulanic acid using polymer-based aqueous two-phase systems

Pereira

Santos

Johansson

et al. 2012

Separation and Purification Technology

Self Cite

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“…A different approach considers the use of aqueous two-phase micellar systems (ATPMS). Those are micellar solutions that separate spontaneously in two phases: a micelle-rich phase and a micelle‑poor phase, depending on operating conditions (pH, ionic strength, and temperature) [ 196 ]. An ATPMS employing the surfactant n-decyltetraethylene oxide showed preferential partition of proteins towards the micelle-rich phase, but if a denaturation step is applied prior to extraction, the 52% of CA is recovered in this phase [ 196 ].…”

Section: Downstream Processing Of Camentioning

confidence: 99%

“…Those are micellar solutions that separate spontaneously in two phases: a micelle-rich phase and a micelle‑poor phase, depending on operating conditions (pH, ionic strength, and temperature) [ 196 ]. An ATPMS employing the surfactant n-decyltetraethylene oxide showed preferential partition of proteins towards the micelle-rich phase, but if a denaturation step is applied prior to extraction, the 52% of CA is recovered in this phase [ 196 ]. ATPMS formed by the non-ionic surfactant Triton X-114 (0.022%) and an anionic one (1%) allowed a CA recovery of 86.3% at 28 °C [ 197 ].…”

Section: Downstream Processing Of Camentioning

confidence: 99%

Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing

2021

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Clavulanic acid (CA) is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by Streptomyces clavuligerus (S. clavuligerus). CA is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria that possess β‑lactam resistance. The clinical importance of CA and the complexity of the production process motivate improvements from an interdisciplinary standpoint by integrating metabolic engineering strategies and knowledge on metabolic and regulatory events through systems biology and multi-omics approaches. In the large-scale bioprocessing, optimization of culture conditions, bioreactor design, agitation regime, as well as advances in CA separation and purification are required to improve the cost structure associated to CA production. This review presents the recent insights in CA production by S. clavuligerus, emphasizing on systems biology approaches, strain engineering, and downstream processing.

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“…Furthermore, Triton X‐100 (TX‐100) has been used in AMTPS for the recovery of pectinase from kesinai plant ( Streblus asper ) leaves . Other nonionic surfactant, n‐decyltetraethylene oxide (C 10 E 4 ) has also been used in the extraction of clavulanic acid from a Streptomyces clavuligerus fermentation broth …”

Section: Introductionmentioning

confidence: 99%

“…25 Other nonionic surfactant, n-decyltetraethylene oxide (C 10 E 4 ) has also been used in the extraction of clavulanic acid from a Streptomyces clavuligerus fermentation broth. 26 The objective of this study was to investigate the feasibility of using TX-100-based AMTPS for the recovery of bacteriocin-like inhibitory substance (BLIS) from a Pediococcus acidilactici Kp10 fermentation broth. The effects of TX-100 concentrations and additives on the partitioning behavior and activity yield of the BLIS in the AMTPS were evaluated.…”

Section: Introductionmentioning

confidence: 99%

Purification of a Bacteriocin‐Like Inhibitory Substance Derived from Pediococcus acidilactici Kp10 by an Aqueous Micellar Two‐Phase System

Jamaluddin

Ariff

Wong

2018

Biotechnology Progress

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Aqueous micellar two‐phase system (AMTPS) is an extractive technique of biomolecule, where it is based on the differential partitioning behavior of biomolecule between a micelle‐rich and a micelle‐poor phase. In this study, an AMTPS composed of a nonionic surfactant, Triton X‐100 (TX‐100) was used for purifying a bacteriocin‐like inhibitory substance (BLIS) derived from Pediococcus acidilactici Kp10. The influences of the surfactant concentration and the effect of additives on the partitioning behavior and activity yield of the BLIS were investigated. The obtained coexistence curves showed that the mixtures of solutions composed of different surfactant concentrations (5–30% w/w) and 50% w/w crude load were able to separate into two phases at temperatures of above 60 °C. The optimum conditions for BLIS partitioning using the TX‐100‐based AMTPS were: TX‐100 concentration of 22.5% w/w, CFCS load of 50% w/w, incubation time of 30 min at 75 °C, and back‐extraction using acetone precipitation. This optimal partitioning resulted in an activity yield of 64.3% and a purification factor of 5.8. Moreover, the addition of several additives, such as sorbitol, KCl, dioctyl sulfosuccinate sodium salt, and Coomassie® Brilliant Blue, demonstrated no improvement in the BLIS separation, except for Amberlite® resin XAD‐4, where the activity yield was improved to 70.3% but the purification factor was reduced to 2.3. Results from this study have demonstrated the potential and applicability of TX‐100‐based AMTPS as a primary recovery method for the BLIS from a complex fermentation broth of P. acidilactici Kp10. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2719, 2019

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Extraction of clavulanic acid using aqueous two‐phase micellar system

Cited by 9 publications

References 22 publications

A stable liquid–liquid extraction system for clavulanic acid using polymer-based aqueous two-phase systems

A stable liquid–liquid extraction system for clavulanic acid using polymer-based aqueous two-phase systems

Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing

Purification of a Bacteriocin‐Like Inhibitory Substance Derived from Pediococcus acidilactici Kp10 by an Aqueous Micellar Two‐Phase System

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