2023
DOI: 10.3390/ijms24021767
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Cofactor Engineering for Efficient Production of α-Farnesene by Rational Modification of NADPH and ATP Regeneration Pathway in Pichia pastoris

Abstract: α-Farnesene, an acyclic volatile sesquiterpene, plays important roles in aircraft fuel, food flavoring, agriculture, pharmaceutical and chemical industries. Here, by re-creating the NADPH and ATP biosynthetic pathways in Pichia pastoris, we increased the production of α-farnesene. First, the native oxiPPP was recreated by overexpressing its essential enzymes or by inactivating glucose-6-phosphate isomerase (PGI). This revealed that the combined over-expression of ZWF1 and SOL3 increases α-farnesene production … Show more

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Cited by 7 publications
(6 citation statements)
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“…At present, the primary approaches for the NADPH cofactor engineering in K. phaffii involve overexpressing glucose-6-phosphate dehydrogenase and 6- gluconolactonase. [34] We speculate that KphFDH/V19 can also serve as an endogenous enzyme for NADPH supply in K. phaffii.…”
Section: In Vitro Nadph Regeneration Systemmentioning
confidence: 85%
“…At present, the primary approaches for the NADPH cofactor engineering in K. phaffii involve overexpressing glucose-6-phosphate dehydrogenase and 6- gluconolactonase. [34] We speculate that KphFDH/V19 can also serve as an endogenous enzyme for NADPH supply in K. phaffii.…”
Section: In Vitro Nadph Regeneration Systemmentioning
confidence: 85%
“…Our result was consistent with recent studies that saw a 91% improvement in bisabolene production after zwf deletion (Zhang et al, 2021) and an enhancement in lycopene production after zwf inactivation (Zhou et al, 2013). The PPP is a crucial energy metabolism pathway, and the overexpression of zwf has been associated with increased NADPH supply for α‐farnesene synthesis (Chen et al, 2023). Hence, the inactivation of zwf could limit the availability of NADPH.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to NADPH, an adequate ATP supply is also crucial for increasing the production of terpenes. Chen et al overexpressed the endogenous adenine phosphoribosyltransferase (APRT), resulting in a 9.4% increase in intracellular ATP content, and also improved the yield of α-farnesene by 10.3% [142].…”
Section: Optimization Of the Upstream And Downstream Pathwaysmentioning
confidence: 99%