Sürdürülebilir Kalkınma Amaçları
Yazarlar
- Şahin, Engin(12)
- Özdemir, Akın(7)
- Dertli, Enes(5)
- Bülbül, Ali Savaş(2)
- Taylan, Osman(2)
- Yilmaz, Mustafa Tahsin(2)
- Aksuoğlu, Selmani(1)
- Alamoudi, Rami(1)
- Bakhsh, Ahmed(1)
- Balubaid, Mohammed(1)
- Bayhan, Beyzanur(1)
- El-Obeid, Tahra(1)
- Herrera-Viedma, Enrique(1)
- Kavi, Mervenur(1)
- Serencam, Hüseyin(1)
- Tozlu, Nesrullah(1)
- Çolak, Nida Sezin(1)
Yayınlar
- MakaleAçık Erişim2024Scopus SJRQ1Efficient bioreduction of 4-phenyl-2-butanone to drug precursor (S)-4-phenyl-2-butanol by a whole-cell biocatalyst using a novel hybrid design technique
Bayhan, Beyzanur; Özdemir, Akın; Dertli, Enes; Şahin, Engin
Asymmetric synthesis is a critical tactic in pharmaceutical industries for creating chiral medications as it allows an enantiomer to be obtained in synthetic chemistry. The asymmetric bioreduction processes by biocatalysts have shown significant potential in producing chiral alcohols. The amount of substrate and the production method of the biocatalytic synthesis of (S)-4-phenyl-2-butanol ((S)-2) are not still desired levels. Furthermore, the biocatalytic asymmetric reduction of 4-phenyl-2-butanone (1) to (R)- or (S)-4-phenyl-2-butanol did not use any mathematical modeling techniques. In this study, the asymmetric bioreduction of 1 was carried out in this work employing Lactobacillus paracasei BD71 biocatalyst and a novel hybrid design-based optimization approach. By using the hybrid design technique, the optimal circumstances were discovered to be pH = 7, temperature = 29 °C, incubation period = 66 h, and agitation speed = 189 rpm. Also, the enantiomeric excess (ee) and conversion could be 99.15 % and 98.19 %, respectively. Next, (S)-2 was acquired to be ee: 99 %, conversion: >99 %, and yield: 97 % from the optimum bioreduction conditions. Furthermore, 14.08 g of 1 under optimal conditions was entirely transformed into (S)-2 (13.84 g, 97 % isolated yield). This study is the first research attempt to use a biocatalyst and an innovative and new hybrid design-based optimization approach to fabricate enantiopure (S)-2 at a high gram scale. This work has successfully demonstrated that the new hybrid design-based optimization technique is applicable to biocatalytic asymmetric reduction processes.
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İncele - MakaleAçık Erişim2024Scopus SJRQ1A Multi-response Nonlinear Programming Model with an Inscribed Design to Optimize Bioreduction Conditions of (S)-phenyl (pyridin-2-yl)methanol by Leuconostoc pseudomesenteroides N13
Özdemir, Akın; Şahin, Engin
Asymmetric bioreductions have the potential to synthesize chiral alcohols when catalyzed by biocatalysts. Nevertheless, the (S)-phenyl (pyridin-2-yl)methanol ((S)-2) analgesic synthesis poses significant challenges concerning unsatisfactory substrate amount and production method. Thus, this study proposes an inscribed design-focused multi-response nonlinear optimization model for the asymmetric reduction of the phenyl(pyridin-2-yl)methanone (1) with Leuconostoc pseudomesenteroides N13 biocatalyst. From the novel inscribed design-focused multi-response nonlinear optimization model, optimization conditions of the reaction, such as pH = 6, temperature = 29 °C, incubation time = 53 h, and agitation speed = 153 rpm, were found. Also, the reaction conversion was predicted to be 99%, and the product of the enantiomeric excess (ee) was 98.4% under the obtained optimization conditions. (S)-2 was obtained with 99% ee, 99% conversion, and 98% yield while performing a validation experiment using the determined optimized conditions. In addition, 1 with the amount of 11.9 g was converted entirely to (S)-2 (11.79 g, 98% isolated yield) on a high gram scale. Also, this study is noted as the first example of the gram-scale production of (S)-2 using an optimization strategy and biocatalyst. Further, the applicability of the inscribed design-focused optimization model in biocatalytic reactions has been demonstrated and provides an effective process for the analgesic synthesis of (S)-2, which is a green, cost-effective method of producing chiral aryl heteroaryl methanol.
AtıfScopus3WoS3OpenAlex3İncele - MakaleAçık Erişim2024Scopus SJRQ2Green synthesis of (S)-1-(furan-2-yl)propan-1-ol from asymmetric bioreduction of 1-(furan-2-yl)propan-1-one using whole-cell of Lactobacillus paracasei BD101
Bülbül, Ali Savaş; Şahin, Engin
Chiral heterocyclic alcohols are important precursors for production of pharmaceutical medicines and natural products. (S)-1-(furan-2-yl)propan-1-ol ((S)-2) can be used production of pyranone, which can be used in the synthesis of sugar analogues, antibiotics, tirantamycines, and anticancer drugs. The synthetic approaches for (S)-2, however, have substantial difficulties in terms of inadequate enantiomeric excess (ee) and gram scale synthesis. Moreover, the biocatalytic synthesis of (S)-2 is unknown until now. In this study, the synthesis of (S)-2 was carried out by performing the asymmetric bioreduction of 1-(furan-2-yl)propan-1-one (1) using the Lactobacillus paracasei BD101 biocatalyst obtained from boza, a grain-based fermented beverage. (S)-2 was obtained with >99% conversion, >99% ee, and 96% yield under the optimized conditions. Furthermore, in 50 h, 8.37 g of 1 was entirely transformed into (S)-2 on gram scale (96% isolated yield, 8.11 g). This is the first report on the high-gram scale biocatalyzed synthesis of enantiopure (S)-2. These data suggest that L. paracasei BD101 can be used to bioreduction of 1 in gram scale and efficiently produce (S)-2. Furthermore, these findings laid the base for future study into the biocatalytic production of (S)-2. It was particularly notable as it was the highest known to date optical purity of (S)-2 generated by asymmetric reduction using a biocatalyst. This work offers a productive environmentally friendly method for producing (S)-2 using biocatalysts.
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İncele - MakaleYalnız künye2023Scopus SJRQ2Efficient bioreduction of 1-(furan-2-yl)ethanone into enantiomerically pure drug precursor by Lactobacillus paracasei BD101
Şahin, Engin
Asymmetric bioreduction catalyzed by biocatalyst have shown considerable potential in the preparation of chiral alcohols. (R)-1-(furan-2-yl)ethanol ((R)-2) can be used precursor in the synthesis of many naturally bioactive piperidine alkaloids such as (−)-Cassine, (−)-Spectaline, (−)-Carnavaline, Prosafrine and (−)- Prosafrinine. Moreover, (R)-2 a key chiral precursor in the production of α, β-unsaturated δ- lactones, which have antifungal, antibiotic, and cytotoxic effects on human tumor cells. However, the synthesis routes of (R)-2 still pose significant challenges in term of unsatisfactory enantiomeric excess (ee) and gram scale synthesis. In this study, Lactobacillus paracasei BD101 biocatalyst from boza, a cereal-based fermented beverage, for the asymmetric bioreduction of the 1-(furan-2-yl)ethanone (1). Following biocatalytic process optimization, (R)-2 was generated with >99% ee and 97% yield. In addition, 9.9 g of 1 was completely converted into (R)-2 on a gram scale (9.78 g, 97% isolated yield) in 48 h. This is the first report about the fabrication of enantiopure (R)-2 in high gram scale using biocatalyst. The optical purity of (R)-2 produced by asymmetric reduction with L paracasei BD101 was also noteworthy since it was the highest documented to date. This study provides an efficient green process for the biocatalytic synthesis of (R)-2.
AtıfScopus16WoS15OpenAlex14İncele - MakaleYalnız künye2023Scopus SJRQ3Modified distance optimization method for the asymmetric bioreduction conditions of phenyl(thiophen-2-yl)methanone by Weissella paramesenteroides N7
Özdemir, Akın; Şahin, Engin
Chirality plays a significant part in life since it is closely linked to carrying out the many metabolic processes that make up a living being. Chiral secondary alcohols such as diaryl-, aryl heteroaryl-, and diheteroaryl are employed in pharmaceuticals as drug intermediates. Although biocatalytic asymmetric reduction of prochiral ketones containing aromatic and heteroaromatic groups is widely known, biocatalytic reduction of heteroaromatic prochiral ketones containing sulfur heteroatoms is rarely known. Very few studies exist in the literature, including the biocatalytic reduction of phenyl(thiophen-2-yl)methanone (1). Moreover, the biocatalytic reduction of 1 with a mathematical modelling and optimization technique is unknown until now. In this study, Weissella paramesenteroides N7 biocatalyst for the asymmetric bioreduction of 1 using a novel modified distance optimization method. Optimization conditions were found as pH = 6.46, temperature = 26 °C, incubation period = 71 h, agitation speed = 200 rpm by the modified distance optimization method, and it was determined that the conversion and enantiomeric excess (ee) under these conditions could be 98.7% and 98%, respectively. Under these proposed optimization conditions, (S)-phenyl(thiophen-2-yl)methanol ((S)-2) was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 11.29 g of 1 was completely converted into (S)-2 (11.07 g, 97% isolated yield) under optimized conditions. This is the first report about the fabrication of enantiopure (S)-2 in high gram scale using a biocatalyst and a novel modified distance optimization technique. In this study, the successful applicability of the new modified distance optimization method in biocatalytic asymmetric reduction reactions has been successfully demonstrated.
AtıfScopus3WoS3OpenAlex5İncele - MakaleAçık Erişim2023Scopus SJRQ2Efficient bio-catalytic production of enentiopure (S)-(4-chlorophenyl)(phenyl)methanol as a drug precursor by using a novel rotatable composite design-based optimization strategy
Tozlu, Nesrullah; Bülbül, Ali Savaş; Özdemir, Akın; Şahin, Engin
Asymmetric bioreductions catalyzed by biocatalysts have demonstrated great promise in manufacturing chiral alcohols. On the other hand, the synthesis of (S)-(4-chlorophenyl)(phenyl)methanol ((S)-2), precursors of L-cloprastine and carbinoxamine, still presents considerable challenges due to the inadequate substrate quantity and production process. In this work, a novel rotatable composite design-based optimization technique was used with the Lactobacillus paracasei BD101 biocatalyst for the asymmetric reduction of (4-chlorophenyl)(phenyl)methanone (1). Optimization conditions of the reaction were determined by the proposed optimization strategy as: pH=5.85, temperature=37 °C, incubation time=71 h, and agitation speed=120 rpm. The reaction conversion and the product of enantiomeric excess (ee) were also predicted to be 97% and 99%, respectively. In the experimental study performed under the determined optimized conditions, (S)-2 was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 1 with the amount of 15.166 g was completely converted to (S)-2 (14.85 g, 97% isolated yield) on a high-gram scale. Notice that the manufacture of (S)-2 on a gram scale utilizing a biocatalyst and an optimization technique is demonstrated in this work for the first time. Finally, an economical, effective, and environmentally friendly biocatalytic process for the biocatalytic synthesis of (S)-2, which have antitussive and antiemetic properties and relax the bronchial muscle, has been demonstrated by the novel rotatable composite design-based optimization method.
AtıfScopus3WoS3OpenAlex2İncele - MakaleAçık Erişim2022Scopus SJRQ1Optimization of Asymmetric Bioreduction Conditions of 2-methyl-1-phenylpropan-1-one by Lactobacillus fermentum BY35 Using I-Optimal Design-Based Model
Aksuoğlu, Selmani; Özdemir, Akın; Serencam, Hüseyin; Dertli, Enes; Şahin, Engin
The bioreduction of prochiral ketones offers efficient access to chiral secondary alcohols, which are potentially beneficial precursors for producing many biologically active compounds and natural products. This bioreduction process can be affected by different parameters when whole-cell of biocatalysts such as Lactic Acid Bacteria strains are applied. In this context, this paper proposed an I-optimal design-based model to optimize culture parameters such as temperature, pH, incubation period, and agitation speed for asymmetric bioreduction of 2-methyl-1-phenylpropan-1-one (1) with Lactobacillus fermentum BY35 as a biocatalyst while achieving the highest conversion rate (cr) and enantiomeric excess (ee). The optimum settings of the four culture parameters and the cr and ee values were found using the proposed optimization model as follows: pH = 6.5, temperature = 25 °C, incubation period = 38.5 h, agitation speed = 200 rpm, the ee value = 98.78%, and the cr value = 98.92%. After the validation of the process, the cr and ee values were found to be > 99% and > 99%, respectively, while using the optimum operating conditions from the optimization model. Thus, the results of the optimization model are consistent with the results of the validation experiment. It is also noted that this paper is the first to optimize culture parameters using the proposed I-optimal design-based model for an asymmetric reduction.
AtıfScopus3WoS3OpenAlex3İncele - MakaleYalnız künye2022Scopus SJRQ3Optimization of asymmetric reduction conditions of 2-bromo-1-(naphthalen-2-yl)ethanone by Enterococcus faecium BY48 biocatalyst with A-optimal design-embedded model
Özdemir, Akın; Şahin, Engin
Aromatic α-halohydrins, especially 2-haloethanols, which are a common pharmacological precursor, may be readily transformed to chiral β-adrenergic receptor blockers. Studies including the synthesis of (S)-2-bromo-1-(naphthalen-2-yl)ethanol ((S)-2), an α-halohydrin, in high conversion, enantiomeric excess (ee), and yield by biocatalytic asymmetric reduction of 2-bromo-1-(naphthalen-2-yl)ethanone (1) are still insufficient. Moreover, asymmetric reduction of substrate 1 using a mathematical optimization method is not explored in the current literature. In this article, the four asymmetric bioreduction conditions, which are (1) pH, (2) temperature, (3) incubation period, and (4) agitation speed, of substrate 1 were optimized to obtain (S)-2 with A-optimal design-embedded model in the presence of Enterococcus faecium BY48. Optimum bioreduction conditions were determined by the A-optimal design-embedded model as follows: pH = 7, temperature = 25°C, incubation period = 24 h, and agitation speed = 200 rpm. And then, it was suggested that (S)-2 could be obtained with 98.88% ee and 100% conversion rate (cr) under these optimum conditions. As a result of the experimental reaction performed under the optimization conditions suggested by the model, (S)-2 was obtained with 99% ee and 100% cr. The study revealed that E. faecium BY48 could be used as a biocatalyst in asymmetric reduction reactions. Also, the A-optimal design-embedded model could have the great potential to obtain the optimum asymmetric bioreduction conditions.
AtıfScopus3WoS3OpenAlex4İncele - MakaleAçık Erişim2022Scopus SJRQ1Optimization of Biocatalytic Production of Enantiopure (S)-1-(4-Methoxyphenyl) Ethanol with Lactobacillus senmaizuke Using the Box–Behnken Design-Based Model
Kavi, Mervenur; Özdemir, Akın; Dertli, Enes; Şahin, Engin
Enantiomerically pure (S)-1-(4-methoxyphenyl) ethanol is a significant molecule for the production of various drug intermediates. (S)-1-(4-methoxyphenyl) ethanol was synthesized from 4-methoxyacetophenone using Lactobacillus senmaizuke as a biocatalyst. In addition, optimization of experimental conditions is important to analyze the role of culture parameters for catalytic bioreduction reactions. For this particular purpose, the experimental conditions of pH, incubation period, temperature, and agitation speed were investigated with the Box–Behnken experimental design-based proposed optimization model. (S)-1-(4-methoxyphenyl) ethanol, which can be used for the synthesis of antihistamines, including diphenhydramine hydrochloride and loratadine cycloalkyl [b] indoles that have the treatment function for an allergic response, was obtained in > 99% conversion, > 99% enantiomeric excess and 96% yield with whole cells of L. senmaizukei at this optimization conditions: pH = 5.80, the temperature = 29 °C, incubation period = 50 h, and agitation speed = 155 rpm. The bioreduction of 4-methoxyacetophenone efficiency was importantly affected by the quadratic and linear effects of experimental design parameters. Besides, the results demonstrate the importance of design parameters for catalytic bioreduction reactions. It is also concluded that the results show the effectiveness of the Box–Behnken experimental design-based proposed model to obtain optimum operating conditions of design parameters for catalytic bioreduction reactions.
AtıfScopus4WoS4OpenAlex4İncele - MakaleAçık Erişim2020MACHINE LEARNING APPLICATION FOR OPTIMIZING ASYMMETRICAL REDUCTION OF ACETOPHENONE EMPLOYING COMPLETE CELL OF LACTOBACILLUS SENMAIZUKE AS AN ENVIRONMENTALLY FRIENDLY APPROACH
Taylan, Osman; Yilmaz, Mustafa Tahsin; Balubaid, Mohammed; Alamoudi, Rami; El-Obeid, Tahra; Dertli, Enes; Şahin, Engin; Bakhsh, Ahmed; Herrera-Viedma, Enrique
Recently, optimization of the bioreduction reactions by optimization methodologies has gained special interest as these reactions are affected by several extrinsic factors that should be optimized for higher yields. An important example for these kinds of reactions is the complete cell implications for the bioreduction of prochiral ketones in which the culture parameters play crucial roles. Such biocatalysts provide environmentally friendly and clean methodology to perform reactions under mild conditions with high conversion rates. In the present work, at the first step the Lactobacillus senmaizuke was isolated from sourdough and the complete cell application of Lactobacillus senmaizuke for the bioreduction of acetophenone was optimized by an Artificial Neural networks (ANNs) to achieve the highest enantiomeric excess (EE, %). The culture parameters, pH, temperature, incubation period and agitation speed were the experimental factors that were optimized to maximize EE (%) by machine learning algorithm of Artificial Intelligence modeling and the best conditions to maximize EE (95.5 %) were calculated to be pH of 5.7, temperature of 35 ºC, incubation period of 76 h and agitation speed of 240 rpm with very low sum of squared error value (0.611236 %) to bioreduce acetophenone using complete cell of Lactobacillus senmaizuke as a sourdough isolate GRAS microbial species. Accordingly, The ANN was employed to correctly establish the enantiomeric excess values of the specimen with an average absolute error 0.080739 %.
AtıfScopus3WoS2OpenAlex2İncele - MakaleYalnız künye2019Scopus SJRQ3Response surface methodology as optimization strategy for asymmetric bioreduction of acetophenone using whole cell of Lactobacillus senmaizukei
Çolak, Nida Sezin; Şahin, Engin; Dertli, Enes; Yilmaz, Mustafa Tahsin; Taylan, Osman
Whole cell applications are one of the main methodologies for the bioreduction of prochiral ketones to obtain enantiomerically rich chiral secondary alcohols which are mainly affected by the culture parameters of the whole cell. In this study, whole cell of Lactobacillus senmaizukei as a safe Lactic Acid Bacteria (LAB) was used for the reduction of acetophenone and Response Surface Methodology (RSM) application was used to optimize the culture parameters in terms of temperature, pH, incubation time, and agitation level to obtain the highest enantiomeric excess (ee) and conversion rate. The predicted optimum conditions for the bioreduction with whole cell Lactobacillus senmaizukei were found to be pH of 5.25, temperature of 25 °C, incubation time of 72 hr, and agitation level of 100 rpm. Importantly, the efficiency of the reduction of the acetophenone was significantly affected by the linear and quadratic effects of culture parameters. These findings are important to show the role of culture parameters for the bioreduction reactions and also the efficiency of the RSM technique to optimize these parameters.
AtıfScopus10WoS10OpenAlex11İncele - MakaleAçık Erişim2019Scopus SJRQ3Green synthesis of enantiopure (S)-1-(benzofuran-2-yl)ethanol by whole-cell biocatalyst
Şahin, Engin
Optically active aromatic alcohols are valuable chiral building blocks of many natural products and chiral drugs. Lactobacillus paracasei BD87E6, which was isolated from a cereal-based fermented beverage, was shown as a biocatalyst for the bioreduction of 1-(benzofuran-2-yl) ethanone to (S)-1-(benzofuran-2-yl) ethanol with highly stereoselectivity. The bioreduction conditions were optimized using L. paracasei BD87E6 to obtain high enantiomeric excess (ee) and conversion. After optimization of the bioreduction conditions, it was shown that the bioreduction of 1-(benzofuran-2-yl)ethanone was performed in mild reaction conditions. The asymmetric bioreduction of the 1-(benzofuran-2-yl)ethanone had reached 92% yield with ee of higher than 99.9% at 6.73 g of substrate. Our study gave the first example for enantiopure production of (S)-1-(benzofuran-2-yl)ethanol by a biological green method. This process is also scalable and has potential in application. In this study, a basic and novel whole-cell mediated biocatalytic method was performed for the enantiopure production of (S)-1-(benzofuran-2-yl)ethanol in the aqueous medium, which empowered the synthesis of a precious chiral intermediary process to be converted into a sophisticated molecule for drug production.
AtıfScopus32WoS30OpenAlex34İncele