title: Calmodulin-mediated suppression of 2-ketoisovalerate reductase in Beauveria bassiana beauvericin biosynthetic pathway.
abstract: Ketoisovalerate reductase (KIVR, E.C. 1.2.7.7) mediates the specific reduction of 2-ketoisovalerate (2-Kiv) to d-hydroxyisovalerate (d-Hiv), a precursor for beauvericin biosynthesis. Beauvericin, a famous mycotoxin produced by many fungi, is a cyclooligomer depsipeptide, which has insecticidal, antimicrobial, antiviral, and cytotoxic activities. In this report, we demonstrated that Beauveria bassiana 2-ketoisovalerate reductase (BbKIVR) acts as a typical KIVR enzyme in the entomopathogenic fungus B. bassiana. In addition, we found that BbKIVR interacts with calmodulin (CaM) in vitro and in vivo. The functional role of CaM-binding to BbKIVR was to negatively regulate the BbKIVR activity in B. bassiana. Environmental stimuli such as light and salt stress suppressed BbKIVR activity in B. bassiana. Interestingly, this negative effect of BbKIVR activity by light and salt stress was recovered by CaM inhibitors, suggesting that the inhibitory mechanism is mediated through stimulation of CaM activity. Therefore, this work suggests that BbKIVR plays an important role in the beauvericin biosynthetic pathway mediated by environmental stimuli such as light and salt stress via the CaM signaling pathway.
authors.affiliation: Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon, 404-834, Korea.|Institute of Life Science and Biotechnology, Sungkyunkwan University, Suwon, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon, 404-834, Korea.
authors.forename: Deok-Hyo
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: Junsang
authors.initials: J
authors.lastname: Oh
authors.affiliation: Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Korea.
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Hyun
authors.affiliation: Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Korea.
authors.forename: Jae-Gu
authors.initials: JG
authors.lastname: Han
authors.affiliation: Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon, 404-834, Korea.
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Sung
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D052982:Beauveria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D047630:Depsipeptides / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D045782:Hemiterpenes; D007651:Keto Acids / Q000378:metabolism; D009183:Mycotoxins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D002147:Calmodulin; D047630:Depsipeptides; D005656:Fungal Proteins; D045782:Hemiterpenes; D007651:Keto Acids; D009183:Mycotoxins; C004456:beauvericin; C001505:alpha-ketoisovalerate; D000429:Alcohol Oxidoreductases; C021934:2-dehydropantoate 2-reductase