增强曼德利酸反体的生物生产和加工:为高价值的制药和聚合物应用提供可持续的平台
Hanan Latif Messiha1,2, Alec Banner1,2, Mohamed Amer1,2
1Future Biomanufacturing Research Hub (Future BRH), Manchester Institute of Biotechnology (MIB), 131 Princess Street, Manchester, M1 7DN, UK.
Biotechnology for biofuels and bioproducts
|December 17, 2025
概括
这项研究利用大肠杆菌 (Escherichia coli) 进行了曼德利酸 (MA) 体的高产生物合成,实现了体内标位的创纪录. 综合下游加工确保了高纯度,使这种有价值的性化学品的可持续生产成为可能.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 绿色化学 绿色化学
背景情况:
- 曼德利酸 (MA) 是药品,化品和聚合物的关键性分子.
- 传统的合成方法面临着环境和选择性挑战.
- 微生物生物合成提供了一个可持续的替代方案,但受限于低产量和恢复问题.
研究的目的:
- 为增强 (R) - 和 (S) - 曼酸的酶选择性生物合成设计一种微生物底盘.
- 开发综合下游加工,用于高纯度MA回收.
- 为了验证生物基MA在聚合物合成中的实用性.
主要方法:
- 代谢工程和优化大肠杆菌对MA生产的途径.
- 在定义的最小介质中进行料批发发酵.
- 两步下游加工,包括溶剂提取和结晶.
主要成果:
- 在大肠杆菌中达到最高报告的体内标位:2.9 g/L (R) -MA (99% ee) 和5.7 g/L (S) -MA (93% ee).
- 高纯度MA回收 (>99.0%) 的效率为 (S) -MA的84%和 (R) -MA的77%.
- 从生物基MA中成功合成了SAMA和曼代利德,证明了其功能效用.
结论:
- 从可再生资源中建立了一个强大的微生物平台,用于从可再生资源中进行enantioselective mandelic acid生物合成.
- 代谢工程,下游处理和应用验证的综合方法提供了一个可扩展的生物生产战略.
- 提供一种可持续和环保的途径,以获得高价值的性化学品,与绿色化学和循环生物经济原则保持一致.
相关概念视频
01:14Alkylation of β-Diester Enolates: Malonic Ester Synthesis
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Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.
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02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
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Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
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00:53Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)
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Acyclic diene metathesis polymerization or ADMET polymerization involves cross-metathesis of terminal dienes, such as 1,8-nonadiene, to give linear unsaturated polymer and ethylene. As ADMET is a reversible process, the formed ethylene gas must be removed from the reaction mixture to complete the polymerization process.
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
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02:30Racemic Mixtures and the Resolution of Enantiomers
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A racemic mixture, or racemate, is an equimolar mixture of enantiomers of a molecule that can be separated using their unique interaction with chiral molecules or media. Racemic mixtures are denoted by the (±)- prefix. This ‘optical rotation descriptor’ applies to the whole solution of a racemic mixture rather than a specific stereoisomer. Enantiomers typically have the same physical and chemical properties. Hence, they are not easily separable. However, enantiomers can exhibit...
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02:05Prochirality
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The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
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01:12Stereochemical Effects of Enolization
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The chiral α-carbon of the carbonyl compound is the stereocenter of the molecule. As shown in the figure below, when such a carbonyl compound undergoes racemization under an acidic or basic condition, an achiral enol is formed.
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