title: Enhanced Production of Itaconic Acid through Development of Transformed Fungal Strains ofAspergillus terreus.
abstract: Metabolic engineering with a high-yielding mutant,A. terreusAN37, was performed to enhance the production of itaconic acid (IA). Reportedly, the gene cluster for IA biosynthesis is composed of four genes:reg(regulator),mtt(mitochondrial transporter),cad(cis-aconitate decarboxylase), andmfs(membrane transporter). By overexpressing each gene of the IA gene cluster inA. terreusAN37 transformed by the restriction enzyme-mediated integration method, several transformants showing high productivity of IA were successfully obtained. One of the AN37/cadtransformants could produce a very high amount of IA (75 g/l) in shake-flask cultivations, showing an average of 5% higher IA titer compared with the high-yielding control strain. Notably, in the case of themfstransformants, a maximal increase of 18.3% in IA production was observed relative to the control strain under the identical fermentation conditions. Meanwhile, the overexpression ofregandmttgenes showed no significant improvements in IA production. In summary, the overexpressedcis-aconitate decarboxylase (CAD) and putative membrane transporter (MFS) appeared to have positive influences on the enhanced IA productivity of the respective transformant. The maximal increases of 13.6~18.3% in IA productivity of the transformed strains should be noted, since the parallel mother strain used in this study is indeed a very high-performance mutant that has been obtained through intensive rational screening programs in our laboratory.
authors.affiliation: Green Materials and Process R&BD Group, Korea Institute of Industrial Technology, Cheonan 331822, Republic of Korea.
authors.forename: Woo-Shik
authors.initials: WS
authors.lastname: Shin
authors.affiliation: Green Materials and Process R&BD Group, Korea Institute of Industrial Technology, Cheonan 331822, Republic of Korea.|Department of Chemical and Biological Engineering, Korea University, Seoul 136713, Republic of Korea.
authors.forename: Boonyoung
authors.initials: B
authors.lastname: Park
authors.affiliation: Green Materials and Process R&BD Group, Korea Institute of Industrial Technology, Cheonan 331822, Republic of Korea.|Department of Green Process and System Engineering, Korea University of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Dohoon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Chemical and Biological Engineering, Korea University, Seoul 136713, Republic of Korea.
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Oh
authors.affiliation: College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
authors.forename: Gie-Taek
authors.initials: GT
authors.lastname: Chun
authors.affiliation: Green Materials and Process R&BD Group, Korea Institute of Industrial Technology, Cheonan 331822, Republic of Korea.|Department of Green Process and System Engineering, Korea University of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Kim
mesh_terms: D001230:Aspergillus / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D001709:Biotechnology; D002262:Carboxy-Lyases / Q000235:genetics; D005285:Fermentation; D005656:Fungal Proteins / Q000378:metabolism; D005800:Genes, Fungal; D026901:Membrane Transport Proteins / Q000235:genetics; D060847:Metabolic Engineering / Q000379:methods; D005810:Multigene Family; D009154:Mutation; D011523:Protoplasts; D013386:Succinates / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D014170:Transformation, Genetic
chemical_list: D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D013386:Succinates; D002262:Carboxy-Lyases; C018742:aconitate decarboxylase; C005229:itaconic acid
keywords: Aspergillus terreus; cis-aconitate decarboxylase (CAD); itaconate gene cluster; plasma membrane transporter (MFS); protoplast transformation; restriction enzyme-mediated integration (REMI)