首页> 外文学位 >The bioproduction of l-phenylacetylcarbinol using solid-liquid two phase partitioning bioreactors.
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The bioproduction of l-phenylacetylcarbinol using solid-liquid two phase partitioning bioreactors.

机译:使用固液两相分配生物反应器生物生产l-苯基乙酰甲醇。

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摘要

Biphasic systems such as two-phase partitioning bioreactors (TPPBs) have been used to alleviate biological inhibition by sequestering inhibitory compounds within an immiscible phase. The use of solid polymer beads as this auxiliary phase provides a fully biocompatible alternative to commonly used yet potentially toxic organic solvents. This work focused on the application of solid-liquid TPPBs to the bioproduction of the pharmaceutical precursor L-phenylacetylcarbinol (PAC), a biotransformation which suffers from substrate (benzaldehyde), product (PAC), and by-product (benzyl alcohol) inhibition, and simple strategies to improve TPPB performance in general.;A wide range of commercially available, biocompatible, and non-bioavailable polymers were screened for their affinity for benzaldehyde, PAC, and benzyl alcohol. Hytrel G3548L demonstrated the highest affinity for all three target compounds and was subsequently used in solid-liquid TPPBs for PAC production. Using 15% v/v polymer beads, PAC concentration was increased by 104% and benzyl alcohol concentration decreased by 38% over the single phase control. The delivery of benzaldehyde from polymer beads demonstrated only a 6-8% reduction in mass productivity with improved operational simplicity and reduced operator intervention.;The final objective of this work was to independently investigate various aspects of the aqueous phase composition and determine how each factor affects the partition coefficient of benzaldehyde in Hytrel G3548L. Temperature and pH were observed to have no significant effect on partitioning. Salt and glucose additions increased the partition coefficient by 173% and 30% respectively compared to RO water, while ethanol was found to decrease the partition coefficient from 44 (+/-1.6) to 1 (+/-0.3). These findings may be applied to solid-liquid TPPBs to increase or decrease partitioning as required, leading to improved bioreactor performance.;This work has successfully shown that with careful polymer selection, solid-liquid TPPBs can be used to increase the productivity of a biotransformation without the associated biocompatibility problems that have sometimes been observed with organic solvents. The delivery of inhibitory substrate from the polymer phase was successfully accomplished, which is a novel demonstration in the field of solid-liquid TPPBs for biocatalysis. Finally this work contributes a range of simple strategies to improve the partitioning behavior of solid-liquid TPPBs using the aqueous phase composition.
机译:诸如两相分配生物反应器(TPPB)之类的双相系统已用于通过将抑制性化合物隔离在不混溶相中来缓解生物抑制作用。固体聚合物珠粒作为该辅助相的使用提供了与常用的但有潜在毒性的有机溶剂完全生物相容的替代物。这项工作的重点是将固液TPPB用于药物前体L-苯基乙酰甲醇(PAC)的生物生产,遭受底物(苯甲醛),产物(PAC)和副产物(苄醇)抑制的生物转化,总体上,采用简单的策略来改善TPPB性能。筛选了多种可商购的,生物相容性和非生物利用度的聚合物,以了解它们对苯甲醛,PAC和苯甲醇的亲和力。 Hytrel G3548L对所有三种目标化合物都表现出最高的亲和力,随后被用于PAC的固液TPPB中。与单相对照相比,使用15%v / v聚合物珠,PAC浓度增加了104%,苯甲醇浓度减少了38%。从聚合物珠粒中释放出苯甲醛后,仅显示出批量生产率降低了6%至8%,操作简便性得到了改善,操作员的干预也有所减少。这项工作的最终目标是独立研究水相组成的各个方面,并确定每个因素影响Hytrel G3548L中苯甲醛的分配系数。观察到温度和pH对分配没有明显影响。与RO水相比,添加盐和葡萄糖分别增加了173%和30%的分配系数,而发现乙醇将分配系数从44(+/- 1.6)降低到1(+/- 0.3)。这些发现可应用于固液TPPB,以根据需要增加或减少分配,从而改善生物反应器的性能。;这项工作已成功表明,通过精心选择聚合物,固液TPPB可以用于提高生物转化的生产率。没有有机溶剂有时会出现的相关生物相容性问题。从聚合物相中成功地完成了抑制性底物的输送,这是用于生物催化的固液TPPBs领域中的一个新的例证。最后,这项工作为使用水相组合物改善固液TPPB的分配行为提供了一系列简单的策略。

著录项

  • 作者

    Khan, Tanya Razia.;

  • 作者单位

    Queen's University (Canada).;

  • 授予单位 Queen's University (Canada).;
  • 学科 Engineering Chemical.
  • 学位 M.A.Sc.
  • 年度 2010
  • 页码 101 p.
  • 总页数 101
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:36:43

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