A Point Mutation in ftmD Blocks the Fumitremorgin Biosynthetic Pathway in Aspergillus fumigatus Strain Af293

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Abstract

Fumitremorgins (FTMs), tremorgenic mycotoxins produced by the human pathogen <i>Aspergillus</i> <i>fumigatus</i>, are prenylated indole alkaloids that have been extensively studied in view of their diverse chemical structures and biological activities. Their biosynthetic gene (<i>ftm</i>) cluster was identified on the basis of the genome sequence of <i>A. fumigatus</i>. However, it has been reported that the <i>ftm</i> cluster in genome reference strain Af293 is inactive, which makes complete understanding of the FTM pathway difficult. Hence, we used an FTM-producing strain of <i>A. fumigatus</i>, BM939, to dissect the FTM pathway. Here, we delineate the genetic determinant for the observed defect in the FTM pathway in <i>A. fumigatus</i> Af293. Metabolite profiling and sequence comparison of the two strains revealed a point mutation in <i>ftmD</i> as a possible cause of altered metabolite production in strain Af293. FTM production in Af293 was restored when a DNA fragment containing <i>ftmD</i> from BM939 was introduced. Biochemical analysis indicated that FtmD is a methyltransferase that catalyzes the conversion of 6-hydroxytryprostatin B into tryprostatin A. The mutated FtmD retained enzymatic activity but did not function under physiological conditions, resulting in blockage of the FTM pathway in <i>A. fumigatus</i> Af293.

Journal

  • Bioscience, Biotechnology, and Biochemistry

    Bioscience, Biotechnology, and Biochemistry 77(5), 1061-1067, 2013-05-23

    Japan Society for Bioscience, Biotechnology, and Agrochemistry

References:  38

  • <no title>

    KELLER NP

    Nat. Rev. Microbiol. 3, 937-947, 2005

    Cited by (1)

  • <no title>

    LI SM

    Nat. Prod. Rep. 27, 57-78, 2010

    Cited by (1)

  • <no title>

    WILLIAMS R

    Top. Curr. Chem. 209, 97-173, 2000

    Cited by (1)

  • <no title>

    GRUNDMANN A

    Microbiology 151, 2199-2207, 2005

    Cited by (1)

  • <no title>

    DING Y

    J. Am. Chem. Soc. 132, 12733-12740, 2010

    Cited by (1)

  • <no title>

    COLE RJ

    Handbook of Secondary Fungal Metabolites, 222-232, 2003

    Cited by (1)

  • <no title>

    JAIN HD

    Bioorg. Med. Chem. 16, 4626-4651, 2008

    Cited by (1)

  • <no title>

    KATO N

    Chembiochem 10, 920-928, 2009

    Cited by (1)

  • <no title>

    RABINDRAN SK

    Cancer Res. 58, 5850-5858, 1998

    Cited by (1)

  • <no title>

    RABINDRAN SK

    Cancer Res. 60, 47-50, 2000

    Cited by (1)

  • <no title>

    NIERMAN WC

    Nature 438, 1151-1156, 2005

    Cited by (1)

  • <no title>

    LI SM

    J. Antibiot. 64, 45-49, 2011

    Cited by (1)

  • <no title>

    MAIYA S

    Chembiochem 7, 1062-1069, 2006

    Cited by (1)

  • <no title>

    GRUNDMANN A

    Chembiochem 9, 2059-2063, 2008

    Cited by (1)

  • <no title>

    CUI CB

    J. Antibiot. 49, 527-533, 1996

    Cited by (1)

  • <no title>

    STEFFAN N

    Org. Biomol. Chem. 7, 4082-4087, 2009

    Cited by (1)

  • <no title>

    KATO N

    Chembiochem 12, 711-714, 2011

    Cited by (1)

  • <no title>

    LISCOMBE DK

    Nat. Prod. Rep. 29, 1238-1250, 2012

    Cited by (1)

  • <no title>

    ZUBIETA C

    Nat. Struct. Biol. 8, 271-279, 2001

    Cited by (1)

  • <no title>

    ZUBIETA C

    Plant Cell 14, 1265-1277, 2002

    Cited by (1)

  • <no title>

    JANSSON A

    J. Mol. Biol. 334, 269-280, 2003

    Cited by (1)

  • <no title>

    JANSSON A

    J. Biol. Chem. 279, 41149-41156, 2004

    Cited by (1)

  • <no title>

    WADA K

    J. Mol. Biol. 360, 839-849, 2006

    Cited by (1)

  • <no title>

    COOKE HA

    Biochemistry 48, 9590-9598, 2009

    Cited by (1)

  • <no title>

    SINGH S

    Proteins 79, 2181-2188, 2011

    Cited by (1)

  • <no title>

    FEDOROVA ND

    PLoS Genet. 4, e1000046, 2008

    Cited by (1)

  • <no title>

    BOK JW

    Eukaryot. Cell 4, 1574-1582, 2005

    Cited by (1)

  • <no title>

    TUDZYNSKI B

    Appl. Microbiol. Biotechnol. 66, 597-611, 2005

    Cited by (1)

  • <no title>

    KATO N

    Curr. Opin. Chem. Biol. 16, 101-108, 2012

    Cited by (1)

  • <no title>

    NOIKE M

    PLoS ONE 7, e42090, 2012

    Cited by (1)

  • <no title>

    FRISVAD JC

    Modern Concepts in Penicillium and Aspergillus Classification, 201-208, 1990

    Cited by (1)

  • <no title>

    HONG SB

    Mycologia 97, 1316-1329, 2005

    Cited by (1)

  • <no title>

    BOK JW

    Infect. Immun. 74, 6761-6768, 2006

    Cited by (1)

  • <no title>

    CRAMER RA Jr

    Eukaryot. Cell 5, 972-980, 2006

    Cited by (1)

  • <no title>

    KUPFAHL C

    Mol. Microbiol. 62, 292-302, 2006

    Cited by (1)

  • <no title>

    SPIKES S

    J. Infect. Dis. 197, 479-486, 2008

    Cited by (1)

  • <no title>

    SUGUI JA

    Eukaryot. Cell 6, 1562-1569, 2007

    Cited by (1)

  • <no title>

    ABAD A

    Rev. Iberoam. Micol. 27, 155-182, 2010

    Cited by (1)

Codes

  • NII Article ID (NAID)
    10031177597
  • NII NACSIS-CAT ID (NCID)
    AA10824164
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09168451
  • NDL Article ID
    024526252
  • NDL Call No.
    Z53-G223
  • Data Source
    CJP  NDL  J-STAGE 
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