ArticleMicrobial cell factories2022
Metabolic engineering of Pichia pastoris for myo-inositol production by dynamic regulation of central metabolism.
Article in Microbial cell factories, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 62 citations in OpenAlex.
- Metabolic Engineering of Pichia pastoris for S-Adenosylmethionine Overproduction via Transcriptomic-Guided Energy Reallocation.Biotechnology journal · 2026Article
- Metabolic engineering ofApplied and environmental microbiology · 2026Review
- Multistep metabolic engineering of Pichia pastoris for biosynthesis of N‑acetylneuraminic acid.Applied microbiology and biotechnology · 2026Article
- Rewiring central metabolism in Komagataella phaffii for efficient mannose synthesis.Microbial cell factories · 2025Article
- Balancing Cell Growth and Product Synthesis for Efficient Microbial Cell Factories.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Development of a lysine biosensor for the dynamic regulation of cadaverine biosynthesis in E. coli.Microbial cell factories · 2025Article
- Characterization of MAP c21873-1 as a new counter-selectable marker for unmarked genetic modification of Pichia pastoris.Microbial cell factories · 2024Article
- Cell factories for biosynthesis of D-glucaric acid: a fusion of static and dynamic strategies.World journal of microbiology & biotechnology · 2024Review
- Hansenula polymorpha methanol metabolism genes enhance recombinant protein production in Komagataella phaffi.AMB Express · 2024Article
- Applications of the Methylotrophic YeastJournal of fungi (Basel, Switzerland) · 2024Review
- Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications.Microbial cell factories · 2024Article
- Exploring the potential of myo-inositol in thyroid disease management: focus on thyroid cancer diagnosis and therapy.Frontiers in endocrinology · 2024Review
- A novel CRISPR/Cas9 system with high genomic editing efficiency and recyclable auxotrophic selective marker for multiple-step metabolic rewriting inSynthetic and systems biotechnology · 2023Article
- Advances in the optimization of central carbon metabolism in metabolic engineering.Microbial cell factories · 2023Review
- Engineering Escherichia coli for efficient assembly of heme proteins.Microbial cell factories · 2023Article
- Cofactor Engineering for Efficient Production of α-Farnesene by Rational Modification of NADPH and ATP Regeneration Pathway inInternational journal of molecular sciences · 2023Article
- Molecular mechanism of GylR-mediated regulation of glycerol metabolism inFrontiers in microbiology · 2022Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe methylotrophic budding yeast Pichia pastoris GS115 is a powerful expression system and hundreds of heterologous proteins have been successfully expressed in this strain. Recently, P. pastoris has also been exploited as an attractive cell factory for the production of high-value biochemicals due to Generally Recognized as Safe (GRAS) status and high growth rate of this yeast strain. However, appropriate regulation of metabolic flux distribution between cell growth and product biosynthesis is still a cumbersome task for achieving efficient biochemical production.
resultsIn this study, P. pastoris was exploited for high inositol production using an effective dynamic regulation strategy. Through enhancing native inositol biosynthesis pathway, knocking out inositol transporters, and slowing down carbon flux of glycolysis, an inositol-producing mutant was successfully developed and low inositol production of 0.71 g/L was obtained. The inositol production was further improved by 12.7% through introduction of heterologous inositol-3-phosphate synthase (IPS) and inositol monophosphatase (IMP) which catalyzed the rate-limiting steps for inositol biosynthesis. To control metabolic flux distribution between cell growth and inositol production, the promoters of glucose-6-phosphate dehydrogenase (ZWF), glucose-6-phosphate isomerase (PGI) and 6-phosphofructokinase (PFK1) genes were replaced with a glycerol inducible promoter. Consequently, the mutant strain could be switched from growth mode to production mode by supplementing glycerol and glucose sequentially, leading to an increase of about 4.9-fold in inositol formation. Ultimately, the dissolved oxygen condition in high-cell-density fermentation was optimized, resulting in a high production of 30.71 g/L inositol (~ 40-fold higher than the baseline strain).
conclusionsThe GRAS P. pastoris was engineered as an efficient inositol producer for the first time. Dynamic regulation of cell growth and inositol production was achieved via substrate-dependent modulation of glycolysis and pentose phosphate pathways and the highest inositol titer reported to date by a yeast cell factory was obtained. Results from this study provide valuable guidance for engineering of P. pastoris for the production of other high-value bioproducts.
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