title: Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae.
abstract: (S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Yun
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Suryang
authors.initials: S
authors.lastname: Kwak
authors.affiliation: School of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Soo Rin
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Yong-Cheol
authors.initials: YC
authors.lastname: Park
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: ysjin@illinois.edu.
authors.forename: Yong-Su
authors.initials: YS
authors.lastname: Jin
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul 136-713, Republic of Korea. Electronic address: khekim@korea.ac.kr.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000096:biosynthesis*; D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D061249:Batch Cell Culture Techniques; D053898:Biosynthetic Pathways; D000431:Ethanol / Q000378:metabolism; D005285:Fermentation; D060847:Metabolic Engineering / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism
chemical_list: D000431:Ethanol; D000429:Alcohol Oxidoreductases; C023744:acetoacetyl-CoA reductase; D000101:Acetyl-CoA C-Acetyltransferase; D013869:Thiolester Hydrolases; D020155:3-Hydroxybutyric Acid
keywords: (S)-3-hydroxybutyrate; 3-Hydroxybutyryl-CoA thioesterase; Acetoacetyl-CoA reductase; Acetyl-CoA C-acetyltransferase; Polyhydroxyalkanoate; Saccharomyces cerevisiae