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Updated: Aug 1, 2026

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
Published on: August 14, 2019
Systematic metabolic engineering of an industrial Penicillium citrinum for one-step pravastatin production
Mengyi Xiong1, Zhiqiang Du1, Zehao Fan2
1Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, 266101, China; Qingdao New Energy Shandong Laboratory, Qingdao, Shandong, 266101, China; Shandong Energy Institute, Qingdao, Shandong, 266101, China.
Abstract:
Pravastatin is a widely prescribed cholesterol-lowering drug known for its superior water solubility and favorable pharmacokinetics. However, its industrial production remains constrained by an inefficient two-step fermentation process, particularly the second biotransformation step involving Streptomyces fermentation. In this study, we engineered the industrial mevastatin-producing strain Penicillium citrinum MEFC10 to achieve efficient one-step pravastatin biosynthesis. Through systematic screening and integration of optimal cytochrome P450-redox partner modules, a one-step pravastatin production cell factory was constructed in industrial Penicillium citrinum MEFC10. Next, NADP+-dependent g6pd3 was overexpressed to increase statin biosynthesis via NADPH regeneration. Further manipulation of pathway transcriptional regulator, self-resistance gene and minimization of byproduct formation, a high-performance Pra2.0 strain was constructed. The Pra2.0 strain produced 8.48 g/L pravastatin and 15.06 g/L total statins in a 50-L bioreactor under fed-batch fermentation. This work established a one-step fermentation process for pravastatin production with markedly improved efficiency over the conventional methods. This work not only establishes an efficient, green production route for pravastatin but also provides a versatile engineering framework for the sustainable biosynthesis of other complex fungal polyketides.
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