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Engineering the oleaginous yeast Candida tropicalis for α-humulene overproduction.


ABSTRACT:

Background

α-Humulene is a plant-derived monocyclic sesquiterpenoid with multiple pharmacological activities, and far-reaching potential for the development of new drugs. Currently, the production of α-humulene is typically achieved via plant extraction, which is not sustainable and limited by low yields. The oleaginous yeast Candida tropicalis has recently emerged as a valuable host for producing high-value-added chemicals. However, the potential of C. tropicalis for terpenoid production has not been exploited.

Results

In this study, C. tropicalis was engineered for de novo synthesis of α-humulene from glucose. To improve α-humulene production, the codon-optimised α-humulene synthase gene and the entire endogenous farnesyl diphosphate synthesis pathway were co-overexpressed. Furthermore, bottlenecks in the α-humulene synthase pathway were identified and relieved by overexpressing α-humulene synthase, acetoacetyl-CoA thiolase and NADH-dependent HMG-CoA reductase. Combined with fermentation medium optimisation, the engineered strain produced 195.31 mg/L of α-humulene in shake flasks and 4115.42 mg/L in a bioreactor through fed-batch fermentation, a 253- and 5345-fold increase over the initial production, respectively.

Conclusions

This study demonstrates the potential of C. tropicalis for α-humulene production, and presents a platform for the biosynthesis of other terpenoids.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC9137083 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Engineering the oleaginous yeast Candida tropicalis for α-humulene overproduction.

Zhang Lihua L   Yang Haiquan H   Xia Yuanyuan Y   Shen Wei W   Liu Liming L   Li Qi Q   Chen Xianzhong X  

Biotechnology for biofuels and bioproducts 20220526 1


<h4>Background</h4>α-Humulene is a plant-derived monocyclic sesquiterpenoid with multiple pharmacological activities, and far-reaching potential for the development of new drugs. Currently, the production of α-humulene is typically achieved via plant extraction, which is not sustainable and limited by low yields. The oleaginous yeast Candida tropicalis has recently emerged as a valuable host for producing high-value-added chemicals. However, the potential of C. tropicalis for terpenoid productio  ...[more]

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