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Improving the production efficiency of L-threo-methylsulfonylphenylserine by removing acetaldehyde through aeration

PROCESS BIOCHEMISTRY [2024]
Shaoyang Zhang, Guorong Zhu, Zhixiang Pan, Yi Wei, Zuoming Nie, Qing Sheng, Zhongyi Yang
ABSTRACT

L-threo-methylsulonylphenylserine (L-threo-MSPS) is a crucial intermediate in florphenicol and thiamphenicol synthesis. L-threo-MSPS can be synthesized from L-threonine and p-methylsulfonylbenzaldehyde (p-MSBA) chiral selectively under the catalyse of L-threonine transaldolase . However, the byproduct acetaldehyde formed during the reaction process severely hinders the biosynthesis of high-quality L-threo-MSPS. The accumulated acetaldehyde reacts with L-thero-MSPS and L-threonine to form N-derivatives, and the activity of L-threonine transaldolase decreases to 14.10% even when the concentration of acetaldehyde is as low as 0.5 g/L. The acetaldehyde could be removed by aeration, and the removal efficiency is closely related to the aeration conditions, which was described by the volumetric oxygen transfer coefficient k L a in this paper. Regular aeration through pipes cannot provide enough aeration efficiency, and filters or sintered rods were used to increase the k L a value during the reaction. The residual concentration of acetaldehyde depended on the balance between the formation and removal speed of acetaldehyde. When the optimal enzyme concentration was applied and the k L a value of 5.5 min -1 , the L-threo-MSPS concentration reached 293.28 mM in a 1-L reaction, and the highest conversion reached 90.03%. The need of coenzyme NAD + was cut off in this method, and only one enzyme was applied. Consequently, the reaction was simpler and easier to control.

MATERIALS

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