Metabolic engineering of Saccharomyces cerevisiae to improve 1-hexadecanol production |
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| Affiliation: | 1. Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;2. Departments of Chemistry, Biochemistry, and Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States;1. Micalis Institute, Institut National de la Recherche Agronomique (INRA), AgroParisTech, Université Paris–Saclay, 78350 Jouy-en-Josas, France;2. Department of Bioengineering, Imperial College London, London SW7 2AZ, UK;1. Mediterranean Agronomic Institute of Chania, P.O. Box 85, Chania 73100, Greece;2. Institute of Applied Biosciences – Centre for Research and Technology Hellas (INAB-CERTH), P.O. Box 60361, Thermi, 57001 Thessaloniki, Greece;3. Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece;4. Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;5. Department of Biochemistry, School of Medicine, University of Crete, P.O. Box 2208, Heraklion 71003, Greece;1. Amity Institute of Biotechnology, Amity University, NOIDA Sec 125, Uttar Pradesh 201313, India;2. International Centre For Genetic Engineering And Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, Delhi 110067, India |
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| Abstract: | Fatty alcohols are important components of a vast array of surfactants, lubricants, detergents, pharmaceuticals and cosmetics. We have engineered Saccharomyces cerevisiae to produce 1-hexadecanol by expressing a fatty acyl-CoA reductase (FAR) from barn owl (Tyto alba). In order to improve fatty alcohol production, we have manipulated both the structural genes and the regulatory genes in yeast lipid metabolism. The acetyl-CoA carboxylase gene (ACC1) was over-expressed, which improved 1-hexadecanol production by 56% (from 45 mg/L to 71 mg/L). Knocking out the negative regulator of the INO1 gene in phospholipid metabolism, RPD3, further enhanced 1-hexadecanol production by 98% (from 71 mg/L to 140 mg/L). The cytosolic acetyl-CoA supply was next engineered by expressing a heterologous ATP-dependent citrate lyase, which increased the production of 1-hexadecanol by an additional 136% (from 140 mg/L to 330 mg/L). Through fed-batch fermentation using resting cells, over 1.1 g/L 1-hexadecanol can be produced in glucose minimal medium, which represents the highest titer reported in yeast to date. |
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| Keywords: | Fatty alcohol Yeast Regulator Phospholipid Acetyl-CoA Metabolic engineering |
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