ONE-POT FERMENTATION PROCESS FOR SIMVASTATIN PRODUCTION

摘要

Simvastatin is a drug used in treatment of hypercholesterolemia because of its inhibitory activities towards cholesterol biosynthesis. The technology described herein is a novel method of biosynthesizing Simvastatin directly from an engineered microbial host (such as Saccharomyces cerevisiae) using an engineered biosynthetic pathway. The identification and engineering of Aspergillus terreus biosynthetic pathways opens up new metabolic engineering opportunities for statin production from organisms such as yeast. Using this technology, Simvastatin can be obtained by feeding a simple synthetic building block to fermented culture. Such methods provide a cost-effective way of obtaining Simvastatin including, for example, one-pot fermentation processes.

主权项

1. A method of making simvastatin comprising the steps of:
(1) combining a microbial host organism with a 2,2-dimethylbutyryl donor compound, wherein:
(a) the microbial host organism comprises genes expressing LovA (SEQ ID NO: 1), LovB (SEQ ID NO: 2), LovC (SEQ ID NO: 3), LovD (SEQ ID NO: 4), LovG (SEQ ID NO: 5), and cytochrome P450 oxidoreductase (SEQ ID NO: 1);(b) two or more genes in (a) are not naturally expressed by the microbial host organism; and(c) the microbial host organism produces monacolin J; and (2) allowing LovD to transfer the dimethylbutyryl_group from the 2,2-dimethylbutyryl donor compound to regioselectively acylate the C8 hydroxyl group of monacolin J; so that simvastatin is made.