ArticleBioprocess and biosystems engineering2024
Pathway reconstruction and metabolic engineering for the de novo and enhancing production of monacolin J in Pichia pastoris.
Article in Bioprocess and biosystems engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Black yeasts are efficient heterologous hosts for the production of a wide range of fungal polyketides.Nature chemical biology · 2026Article
- Rewiring central metabolism in Komagataella phaffii for efficient mannose synthesis.Microbial cell factories · 2025Article
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5 authors.
Funding
Abstract
The statin is the primary cholesterol-lowering drug. Monacolin J (MJ) is a key intermediate in the biosynthetic pathway of statin. It was obtained in industry by the alkaline hydrolysis of lovastatin. The hydrolysis process resulted in multiple by-products and expensive cost of wastewater treatment. In this work, we used Pichia pastoris as the host to produce the MJ. The biosynthesis pathway of MJ was built in P. pastoris. The stable recombinant strain MJ2 was obtained by the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 genome-editing tool, and produced the MJ titer of 153.6 ± 2.4 mg/L. The metabolic engineering was utilized to enhance the production of MJ, and the fermentation condition was optimized. The MJ titer of 357.5 ± 5.0 mg/L was obtained from the recombinant strain MJ5-AZ with ATP-dependent citrate lyase (ACL), glucose-6-phosphate dehydrogenase (ZWF1) and four lovB genes, 132.7% higher than that from the original strain MJ2. The recombinant strain MJ5-AZ was cultured in a 7-L fermenter, and the MJ titer of 1493.0 ± 9.2 mg/L was achieved. The results suggested that increasing the gene dosage of rate-limiting step in the biosynthesis pathway of chemicals could improve the titer of production. It might be applicable to the production optimization of other polyketide metabolites.
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