A heptaketide naphthaldehyde produced by a polyketide synthase from Nectria haematococca.
Bostrycoidin and fusarubin are biologically active fungal polyketides produced by Nectria haematococca. This azaanthraquinone and naphthoquinone are thought to be biosynthesized via formation of a C(14) heptaketide aldehyde as a common key intermediate. A BLAST search against the genome of N. haematococca revealed one candidate gene (NECHADRAFT_101778, NhPKS1), which encodes a multi-domain polyketide synthase (PKS) with a thiol reductase (TR) domain that would facilitate the reductive release of the intermediate to produce a free aldehyde. To investigate the possible involvement of NhPKS1 in the biosynthesis of bostrycoidin and fusarubin, NhPKS1 was heterologously expressed in Aspergillus oryzae, and shown to produce a heptaketide 3-acetonyl-1,6,8-trihydroxy-2-naphthaldehyde as a single product. Thus, NhPKS1 catalyzes a C-2/C-11 and C-4/C-9 aldol-type cyclization of a linear intermediate followed by a subsequent reductive product release to yield the naphthaldehyde. The results indicate NhPKS1 is the enzyme involved in the biosynthesis of bostrycoidin and fusarubin.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takayoshi
T
Awakawa
Takuya
T
Kaji
Toshiyuki
T
Wakimoto
Ikuro
I
Abe
D000447:Aldehydes / Q000378:metabolism*; D001236:Aspergillus oryzae / Q000378:metabolism; D003500:Cyclization; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism*; D009285:Naphthoquinones / Q000378:metabolism; D055330:Nectria / Q000201:enzymology*; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000447:Aldehydes; D007546:Isoquinolines; D009097:Multienzyme Complexes; D009281:Naphthalenes; D009285:Naphthoquinones; D011994:Recombinant Proteins; C060461:bostrycoidin; C018686:2-naphthaldehyde; D048630:Polyketide Synthases