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Volume 39 Issue 11
Nov.  2012
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Amplification of an MFS Transporter Encoding Gene penT Significantly Stimulates Penicillin Production and Enhances the Sensitivity of Penicillium chrysogenum to Phenylacetic Acid

doi: 10.1016/j.jgg.2012.08.004
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  • Corresponding author: E-mail address: liug@im.ac.cn (Gang Liu)
  • Received Date: 2012-06-18
  • Accepted Date: 2012-08-27
  • Rev Recd Date: 2012-08-09
  • Available Online: 2012-09-07
  • Publish Date: 2012-11-20
  • Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosynthetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames (ORFs) were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them (penT) was selected and cloned. The deduced protein of penT belongs to the major facilitator superfamily (MFS) and contains 12 transmembrane spanning domains (TMS). During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid (PAA) and phenoxyacetic acid (POA). Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenum doubled the penicillin production and enhanced the sensitivity ofP. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane.
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  • [1]
    Aharonowitz, Y., Cohen, G., Martín, J.F. Penicillin and cephalosporin biosynthetic genes: structure, organization, regulation and evolution Annu. Rev. Microbiol., 46 (1992),pp. 461-496
    [2]
    Alenquer, M., Tenreiro, S., Sá-Correia, I. Adaptive response to the antimalarial drug artesunate in yeast involves Pdr1p/Pdr3p-mediated transcriptional activation of the resistance determinants TPO1 and PDR5 FEMS Yeast Res., 6 (2006),pp. 1130-1139
    [3]
    Andrade, A.C., Van Nistelrooy, J.G., Peery, R.B. et al. Mol. Gen. Genet., 263 (2000),pp. 966-977
    [4]
    Barredo, J.L., van Solingen, P., Díez, B. et al. Gene, 83 (1989),pp. 291-300
    [5]
    Brakhage, A.A. Molecular regulation of β-lactam biosynthesis in filamentous fungi Microbiol. Mol. Biol. Rev., 62 (1998),pp. 547-585
    [6]
    Brakhage, A.A., Spröte, P., Al-Abdallah, Q. et al. Regulation of penicillin biosynthesis in filamentous fungi Adv. Biochem. Eng. Biotechnol., 88 (2004),pp. 45-90
    [7]
    Brakhage, A.A., Thön, M., Spröte, P. et al. Aspects on evolution of fungal beta-lactam biosynthesis gene clusters and recruitment of trans-acting factors Phytochemistry, 70 (2009),pp. 1801-1811
    [8]
    Cantoral, J.M., Díez, B., Barredo, J.L. et al. Nat. Biotechnol, 5 (1987),pp. 494-497
    [9]
    Carr, L.G., Skatrud, P.L., Scheetz, M.E. et al. Gene, 48 (1986),pp. 257-266
    [10]
    del Sorbo, G., Schoonbeek, H.J., de Waard, M.A. Fungal transporters involved in efflux of natural toxic compounds and fungicides Fungal Genet. Biol., 30 (2000),pp. 1-15
    [11]
    Díez, B., Gutiérrez, S., Barredo, J.L. et al. J. Biol. Chem., 265 (1990),pp. 16358-16365
    [12]
    Douma, R.D., Deshmukh, A.T., de Jonge, L.P. et al. Biotechnol. Prog., 28 (2012),pp. 337-348
    [13]
    Elander, R.P. Industrial production of β-lactam antibiotics Appl. Microbiol. Biotechnol., 61 (2003),pp. 385-392
    [14]
    Eriksen, S.H., Soderblom, T.B., Jensen, B. et al. Biotechnol. Bioeng., 60 (1998),pp. 310-316
    [15]
    García-Estrada, C., Vaca, I., Lamas-Maceiras, M. et al. Appl. Microbiol. Biotechnol., 76 (2007),pp. 169-182
    [16]
    Harris, D.M., van der Krogt, Z.A., Klaassen, P. et al. BMC Genomics, 10 (2009),p. 75
    [17]
    Hillenga, D.J., Versantvoort, H.J.M., Vandermolen, S. et al. Appl. Environ. Microbiol., 61 (1995),pp. 2589-2595
    [18]
    Kiel, J.A., van den Berg, M.A., Fusetti, F. et al. Funct. Integr. Genomics, 9 (2009),pp. 167-184
    [19]
    Liu, G., Tian, Y., Yang, H. et al. Mol. Microbiol., 55 (2005),pp. 1855-1866
    [20]
    Livak, K.J., Schmittgen, T.D. Methods, 25 (2001),pp. 402-408
    [21]
    Martín, J.F., Casqueiro, J., Kosalková, K. et al. Penicillin and cephalosporin biosynthesis: mechanism of carbon catabolite regulation of penicillin production Antonie Van Leeuwenhoek, 75 (1999),pp. 21-31
    [22]
    Matín, J.F., Casqueiro, J., Liras, P. Secretion systems for secondary metabolites: how producer cells send out messages of intercellular communication Curr. Opin. Microbiol., 8 (2005),pp. 282-293
    [23]
    Martín, J.F., Ullán, R.V., García-Estrada, C. Role of peroxisomes in the biosynthesis and secretion of β-lactams and other secondary metabolites J. Ind. Microbiol. Biotechnol., 39 (2012),pp. 367-382
    [24]
    Mullins, E.D., Chen, X., Romaine, P. et al. Phytopathology, 91 (2001),pp. 173-180
    [25]
    Neyfakh, A.A. Mystery of multidrug transporters: the answer can be simple Mol. Microbiol., 44 (2002),pp. 1123-1130
    [26]
    Nijland, J.G., Kovalchuk, A., van den Berg, M.A. et al. Fungal Genet. Biol., 45 (2008),pp. 1415-1421
    [27]
    Roze, L.V., Chanda, A., Linz, J.E. Compartmentalization and molecular traffic in secondary metabolism: a new understanding of established cellular processes Fungal Genet. Biol., 48 (2011),pp. 35-48
    [28]
    Sá-Correia, I., dos Santos, S.C., Teixeira, M.C. et al. Trends Microbiol., 17 (2008),pp. 22-31
    [29]
    Schmidt, F.R.
    [30]
    Teijeira, F., Ullán, R.V., Guerra, S.M. et al. The transporter CefM involved in translocation of biosynthetic intermediates is essential for cephalosporin production Biochem. J., 418 (2009),pp. 113-124
    [31]
    Teijeira, F., Ullán, R.V., Fernández-Aguado, M. et al. Metab. Eng., 13 (2011),pp. 532-543
    [32]
    Ullán, R.V., Liu, G., Casqueiro, J. et al. Mol. Genet. Genomics, 267 (2002),pp. 673-683
    [33]
    Ullán, R.V., Godio, R.P., Teijeira, F. et al. J. Microbiol. Methods, 75 (2008),pp. 209-218
    [34]
    van de Kamp, M., Driessen, A.J.M., Konings, W.N. Compartmentalization and transport in β-lactam antibiotic biosynthesis by filamentous fungi Antonie Van Leeuwenhoek, 75 (1999),pp. 41-78
    [35]
    van den Berg, M.A., Albang, R., Albermann, K. et al. Nat. Biotechnol., 26 (2008),pp. 1161-1168
    [36]
    Wang, F.Q., Liu, J., Dai, M. et al. Biochem. Biophys. Res. Commun., 360 (2007),pp. 453-458
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