The Biosynthetic Pathway and Sources of Monacolin K

The Biosynthetic Pathway and Sources of Red Yeast Extract Monacolin K

There are few studies about the biosynthetic pathway of monacolin K generated by Monascus purpureus, it is just speculated that this pathway may be similar to the synthetic pathway of monacolin K in Aspergillus terreus [39]. Aspergillus terreus has been frequently utilized to figure out the synthesis of monacolin K [40]. The synthetic pathway of monacolin K in Aspergillus terreus, shown in Figure 4 is as follows: (1) the lovastatin nonaketide synthase (LNKS) catalyzes the synthesis of one molecule of malonyl CoA in condensation reaction with nine molecules of acetyl CoA, generating dihydromonacolin L (a nonaketide compound) that is a main structure of monacolin K, then it formed monacolin L by oxidation, dehydration, and other steps, and finally monacolin J is generated through single oxygenase catalytic hydroxylation reaction; (2) the lovastatin diketide synthase (LDKS) catalyzes the condensation of one molecule of malonyl CoA with two molecules of acetyl CoA to form methylbutyryl CoA; (3) under the action of the transesterase, methylbutyryl CoA is linked to monacolin J with an ester ether bond to complete the synthesis of monacolin K.

Red Yeast Rice Extract Manufacture — The biosynthetic pathway of Monacolin K

Meanwhile, commercial lovastatin appeared as a lipid-lowering drug in the pharmaceutical market with the permission of the FDA in 1986. The sources of commercial lovastatin mainly contain two synthetic approaches. The first is that utilize submerged fermentation (SmF) of Monascus purpureus and Aspergillus terreus, adding carbon and nitrogen source (such as glucose, oat meal, and corn steep liquor) to medium with Monascus purpureus and Aspergillus terreus, after appropriate fermentation, then obtaining lovastatin via separation and purification; the other is chemical synthesis, replacing the decaline ring of the fungal compounds with an aromatic ring, like fluvastatin and atorovastatin [41,42]. Early studies have shown that the structure of monacolin K is chemically identical to that of commercial lovastatin [32].

In common RED YEAST RICE EXTRACT (RYR), monacolin K cannot be produced or is very tiny in a short and simple process of fermentation. Recently researchers reported that commercial lovastatin is added to common RED YEAST RICE EXTRACT (RYR) to imitate functional RED YEAST RICE EXTRACT (RYR) and therefore obtain more profits [43,44]. This phenomenon has inhibited the development of functional RED YEAST RICE EXTRACT (RYR), and more important, long-term use of lovastatin probably can cause burnout, gastrointestinal reactions, myalgia, etc. About 10–15% patients with dyslipidemia who take statins experience skeletal muscle problems [11].

Molecules. 2019 May; 24(10): 1944.
Published online 2019 May 20. doi: 10.3390/molecules24101944
PMCID: PMC6572552
PMID: 31137594
Quality and Authenticity Control of Functional Red Yeast Rice—A Review
Jiawen Song,† Jia Luo,† Zubing Ma, Qiang Sun, Chunjie Wu,* and Xiaofang Li*

Why Red-Life™-Red Yeast Rice Extract (monacolin-K)?