The present invention relates to an enzymatic process for producing cytidine diphosphate choline (hereinafter referred to as CDP-choline) which is useful as a medicine.
CDP-choline is a biosynthetic intermediate for phosphatidyl choline (lecithin), which is a phospholipid, and is useful for the treatment of head injuries, disturbance of consciousness following cerebral surgery, Parkinson's disease, postapoplectic hemiplegia, etc.
Two kinds of processes are known for producing CDP-choline: chemical synthetic processes disclosed in Japanese Published Examined Patent Applications Nos. 6541/64, 1384/67, 6558/88, etc.; and enzymatic processes utilizing cells of microorganisms such as yeast disclosed in Japanese Published Examined Patent Applications Nos. 2358/73, 40757/73 and 40758/73 and Japanese Published Unexamined Patent Applications Nos. 109996/78, 14593/79 and 313594/88.
A feature common to these known processes is the use of cytosine nucleotides such as cytidine-5′-monophosphate (hereinafter referred to as CMP), cytidine-5′-diphosphate (hereinafter referred to as CDP), cytidine-5′-triphosphate (hereinafter referred to as CTP), and cytosine, or their precursors as starting materials.
Of these starting materials, the basic starting material, CMP, is mainly produced by the RNA (ribonucleic acid) decomposition method which provides four types of nucleotides at the same time. This method is inefficient in that it is impossible to selectively obtain CMP.