Christine A. S. Skovbjerg
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Christine A. S. Skovbjerg has a total of 13 co-authors. Here are the top co-authors by number of shared publications:
Bin Qiao
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China
1 shared publication- Chun Li
Department of Chemical Engineering, Key Laboratory for Industrial Biocatalysis of Ministry of Education, Tsinghua University, Beijing, China
1 shared publication - Hala A. Iqbal
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, USA
1 shared publication Hong Liu
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China
1 shared publication- Jef D. Boeke
Institute for Systems Genetics, Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, USA
1 shared publication Jens Christian Nielsen
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
1 shared publication
Latest Publications
- Open Access
- 3 December 2020
- Published by Springer Nature in Nature Communications
- Vol. 11 (1) , 1-10
Pathway engineering in yeast for synthesizing the complex polyketide bikaverin
Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.
- 3 December 2020
- Published by Springer Nature in Nature Communications
- Vol. 11 (1) , 1-10
Open AccessPathway engineering in yeast for synthesizing the complex polyketide bikaverin
Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.