title: Metabolic evolution and (13) C flux analysis of a succinate dehydrogenase deficient strain of Yarrowia lipolytica.
abstract: Bio-based succinic acid production can redirect industrial chemistry processes from using limited hydrocarbons to renewable carbohydrates. A fermentation process that does not require pH-titrating agents will be advantageous to the industry. Previously, a Yarrowia lipolytica strain that was defective for succinate dehydrogenase was constructed and was found to accumulate up to 17.5 g L(-1) of succinic acid when grown on glycerol without buffering. Here, a derivative mutant was isolated that produced 40.5 g L(-1) of succinic acid in 36 h with a yield of 0.32 g g(-1) glycerol. A combination approach of induced mutagenesis and metabolic evolution allowed isolation of another derivative that could utilize glucose efficiently and accumulated 50.2 g L(-1) succinic acid in 54 h with a yield of 0.43 g g(-1) . The parent strain of these isolated mutants was used for [1,6-(13) C2 ]glucose assimilation analysis. At least 35% glucose was estimated to be utilized through the pentose phosphate pathway, while ≥84% succinic acid was formed through the oxidative branch of the tricarboxylic acid cycle. Biotechnol. Bioeng. 2016;113: 2425-2432. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia. t_yuzbashev@genetika.ru.
authors.forename: Tigran V
authors.initials: TV
authors.lastname: Yuzbashev
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Pavel Yu
authors.initials: PY
authors.lastname: Bondarenko
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Sobolevskaya
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Evgeniya Yu
authors.initials: EY
authors.lastname: Yuzbasheva
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Laptev
authors.affiliation: N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Kachala
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Fedorov
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Vybornaya
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Larina
authors.affiliation: Biological Resource Center Russian National Collection of Industrial Microorganisms (BRC VKPM), State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1-st Dorozhny pr., 1, Moscow 117545, Russia.
authors.forename: Sergey P
authors.initials: SP
authors.lastname: Sineoky
mesh_terms: D002247:Carbon Isotopes / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism; D008657:Metabolic Clearance Rate; D064688:Metabolic Flux Analysis / Q000379:methods*; D013385:Succinate Dehydrogenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism*; D025062:Yarrowia / Q000502:physiology*
chemical_list: D002247:Carbon Isotopes; D019802:Succinic Acid; D013385:Succinate Dehydrogenase; D005947:Glucose
keywords: SDH2; Yarrowia lipolytica; low pH; metabolic evolution; succinic acid