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Development of an Improved Amino Ester Hydrolase for Continuous Reactive Crystallization of Beta-Lactam Antibiotics
Development of an Improved Amino Ester Hydrolase for Continuous Reactive Crystallization of Beta-Lactam Antibiotics
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105552
- ISBN
- 9798265401243
- DDC
- 615.329
- 서명/저자
- Development of an Improved Amino Ester Hydrolase for Continuous Reactive Crystallization of Beta-Lactam Antibiotics
- 발행사항
- [Sl] : Georgia Institute of Technology, 2023
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2023
- 형태사항
- 306 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
- 주기사항
- Advisor: Bommarius, Andreas S.;Grover, Martha A.
- 학위논문주기
- Thesis (Ph.D.)--Georgia Institute of Technology, 2023.
- 초록/해제
- 요약α-amino ester hydrolases (AEH) are a class of enzymes that are capable ofsynthesizing β-lactam antibiotics but are less studied than the industrially used penicillinG acylase (PGA). While both classes of enzymes synthesize a variety of β-lactamantibiotics, AEHs are promising candidates for enzymatic synthesis of cephalexin due totheir rapid kinetics and low pH optimum of activity but suffer from low thermostabilityand substrate inhibition. The goal of this thesis is to further develop a thermostable AEHoptimized for synthesis of β-lactam antibiotics and demonstrate a pilot plant for enzymaticreactive crystallization of both amoxicillin and cephalexin. While the pilot plant wasdesigned using PGA, further development of a stable AEH allows for future testing of AEHin a continuous reactive crystallization process. AEH kinetics were first characterized inbatch reactions, and a kinetic model was developed to describe cephalexin synthesis(Chapter 2). The relationships between AEH solution stability, oligomericity, anddeactivation were analyzed (Chapter 3). Using the kinetic model developed in Chapter 2,reactor designs were modelled and evaluated for AEH-catalyzed synthesis of cephalexin(Chapter 4). An improved AEH was developed to address low thermostability usingcomputationally guided rational design (Chapter 5). Using PGA, a pilot plant wasdeveloped for the enzymatic reactive crystallization of both cephalexin and amoxicillin(Chapter 6), and a novel magnetic separation system was developed to recycle immobilizedPGA and isolate pure crystalline API (Chapter 7).
- 일반주제명
- Antibiotics
- 일반주제명
- Magnetic fields
- 일반주제명
- Binding sites
- 일반주제명
- Microscopy
- 일반주제명
- Crystallization
- 일반주제명
- Design
- 일반주제명
- Kinetics
- 일반주제명
- Crystals
- 일반주제명
- Pharmaceutical sciences
- 일반주제명
- Electromagnetics
- 기본자료저록
- Dissertations Abstracts International. 87-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008260126s2023 us c eng d■001000017360593
■00520260202105552
■006m o d
■007cr#unu||||||||
■020 ▼a9798265401243
■035 ▼a(MiAaPQ)AAI32315790
■035 ▼a(MiAaPQ)GeorgiaTech75123
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a615.329
■1001 ▼aLagerman, Colton.
■24510▼aDevelopment of an Improved Amino Ester Hydrolase for Continuous Reactive Crystallization of Beta-Lactam Antibiotics
■260 ▼a[Sl]▼bGeorgia Institute of Technology▼c2023
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2023
■300 ▼a306 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-05, Section: B.
■500 ▼aAdvisor: Bommarius, Andreas S.;Grover, Martha A.
■5021 ▼aThesis (Ph.D.)--Georgia Institute of Technology, 2023.
■520 ▼aα-amino ester hydrolases (AEH) are a class of enzymes that are capable ofsynthesizing β-lactam antibiotics but are less studied than the industrially used penicillinG acylase (PGA). While both classes of enzymes synthesize a variety of β-lactamantibiotics, AEHs are promising candidates for enzymatic synthesis of cephalexin due totheir rapid kinetics and low pH optimum of activity but suffer from low thermostabilityand substrate inhibition. The goal of this thesis is to further develop a thermostable AEHoptimized for synthesis of β-lactam antibiotics and demonstrate a pilot plant for enzymaticreactive crystallization of both amoxicillin and cephalexin. While the pilot plant wasdesigned using PGA, further development of a stable AEH allows for future testing of AEHin a continuous reactive crystallization process. AEH kinetics were first characterized inbatch reactions, and a kinetic model was developed to describe cephalexin synthesis(Chapter 2). The relationships between AEH solution stability, oligomericity, anddeactivation were analyzed (Chapter 3). Using the kinetic model developed in Chapter 2,reactor designs were modelled and evaluated for AEH-catalyzed synthesis of cephalexin(Chapter 4). An improved AEH was developed to address low thermostability usingcomputationally guided rational design (Chapter 5). Using PGA, a pilot plant wasdeveloped for the enzymatic reactive crystallization of both cephalexin and amoxicillin(Chapter 6), and a novel magnetic separation system was developed to recycle immobilizedPGA and isolate pure crystalline API (Chapter 7).
■590 ▼aSchool code: 0078.
■650 4▼aAntibiotics
■650 4▼aMagnetic fields
■650 4▼aBinding sites
■650 4▼aMicroscopy
■650 4▼aCrystallization
■650 4▼aDesign
■650 4▼aKinetics
■650 4▼aCrystals
■650 4▼aPharmaceutical sciences
■650 4▼aElectromagnetics
■690 ▼a0389
■690 ▼a0572
■690 ▼a0607
■71020▼aGeorgia Institute of Technology.
■7730 ▼tDissertations Abstracts International▼g87-05B.
■790 ▼a0078
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360593▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
