PMID- 27449895 OWN - NLM STAT- MEDLINE DCOM- 20170807 LR - 20191210 IS - 1462-2920 (Electronic) IS - 1462-2912 (Linking) VI - 18 IP - 11 DP - 2016 Nov TI - Calmodulin-mediated suppression of 2-ketoisovalerate reductase in Beauveria bassiana beauvericin biosynthetic pathway. PG - 4136-4143 LID - 10.1111/1462-2920.13461 [doi] AB - 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. CI - (c) 2016 Society for Applied Microbiology and John Wiley & Sons Ltd. FAU - Kim, Jiyoung AU - Kim J AD - Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon, 404-834, Korea. AD - Institute of Life Science and Biotechnology, Sungkyunkwan University, Suwon, Korea. FAU - Yoon, Deok-Hyo AU - Yoon DH AD - Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon, 404-834, Korea. FAU - Oh, Junsang AU - Oh J AD - College of Pharmacy, Chung-Ang University, Seoul, Korea. FAU - Hyun, Min-Woo AU - Hyun MW AD - Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Korea. FAU - Han, Jae-Gu AU - Han JG AD - Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Korea. FAU - Sung, Gi-Ho AU - Sung GH AD - Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon, 404-834, Korea. LA - eng PT - Journal Article DEP - 20160809 PL - England TA - Environ Microbiol JT - Environmental microbiology JID - 100883692 RN - 0 (Calmodulin) RN - 0 (Depsipeptides) RN - 0 (Fungal Proteins) RN - 0 (Hemiterpenes) RN - 0 (Keto Acids) RN - 0 (Mycotoxins) RN - 26S048LS2R (beauvericin) RN - 759-05-7 (alpha-ketoisovalerate) RN - EC 1.1.- (Alcohol Oxidoreductases) RN - EC 1.1.1.169 (2-dehydropantoate 2-reductase) SB - IM MH - Alcohol Oxidoreductases/genetics/*metabolism MH - Beauveria/enzymology/genetics/*metabolism MH - *Biosynthetic Pathways MH - Calmodulin/genetics/*metabolism MH - Depsipeptides/*biosynthesis MH - Fungal Proteins/genetics/*metabolism MH - Gene Expression Regulation, Fungal MH - Hemiterpenes MH - Keto Acids/metabolism MH - Mycotoxins/*metabolism MH - Protein Binding MH - Signal Transduction EDAT- 2016/07/28 06:00 MHDA- 2017/08/08 06:00 CRDT- 2016/07/25 06:00 PHST- 2016/05/12 00:00 [received] PHST- 2016/07/10 00:00 [revised] PHST- 2016/07/15 00:00 [accepted] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/08/08 06:00 [medline] PHST- 2016/07/25 06:00 [entrez] AID - 10.1111/1462-2920.13461 [doi] PST - ppublish SO - Environ Microbiol. 2016 Nov;18(11):4136-4143. doi: 10.1111/1462-2920.13461. Epub 2016 Aug 9.