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Journal of biotechnology

Journal of biotechnology

IF: 4.09
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High-level living cell production of cytidine-5′-diphosphocholine in metabolically engineered yeast

Published:20 November 2021 DOI: 10.1016/j.jbiotec.2021.08.013 PMID: 34536458
Yanna Ren , Qi Liu , Haifeng Liu , Xiangshan Zhou , Yuanxing Zhang , Menghao Cai

Abstract

Industrial production of neuroprotective drug CDP-choline is accomplished via permeabilized or lysed cell biotransformation because of the inefficient penetration of substrates into intact cells. We previously proposed a novel one-step living cell method for CDP-choline production by engineered yeast, but obtained low titer and molar yield. This study develops a high-production strain with improved molar yield by metabolic engineering strategies. The selective markers previously integrated into host cell were recovered for facilitating genetic modification, which however resulted a strain with improved CDP-choline titer and molar yield to CMP. Knockout of 5′-NT or CDA in CMP sinking pathway but not APY in CTP sinking pathway further improved CDP-choline titer and molar yield to CMP. However, overexpression of seven enzymes in CTP synthetic pathway showed no positive functions. Finally, optimization of CMP and choline phosphate levels for the optimized recombinant strains achieved a high-level CDP-choline of ~30?g/L, which was enhanced by 400% compared to the previous work. Also, the molar yield of CDP-choline to CMP increased from 40% to 84.7%. The titer and molar yield are comparable to the reported permeabilized or lysed cell based biotransformation methods. It represents a novel and competitive paradigm for the potential industrial production of CDP-choline.

Substances (4)

Related products
Procduct Name CAS Molecular Formula Supplier Price
Cytidine 5’-monophosphate 63-37-6 C9H14N3O8P 666 suppliers $12.00-$2250.00
Cytidine 5'-Diphosphocholine 987-78-0 C14H26N4O11P2 439 suppliers $8.00-$5060.00
phosphorylcholine 107-73-3 C5H15ClNO4P 151 suppliers Inquiry
Cytidine triphosphate 65-47-4 C9H16N3O14P3 84 suppliers $189.00-$1183.00

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