title: The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus.
abstract: BACKGROUND
  Aflatoxins (AFs) are potent carcinogenic compounds produced by several Aspergillus species, which pose serious threats to human health. As sugar is a preferred carbohydrate source for AF production, we examined the possibility of using sugar analogs to inhibit AF biosynthesis.
  
  
  RESULTS
  We showed that although D-glucal cannot be utilized by A. flavus as the sole carbohydrate source, it inhibited AF biosynthesis and promoted kojic acid production without affecting mycelial growth when applied to a glucose-containing medium. The inhibition occurred before the production of the first stable intermediate, norsolorinic acid, suggesting a complete inhibition of the AF biosynthetic pathway. Further studies showed that exogenous D-glucal in culture led to reduced accumulation of tricarboxylic acid (TCA) cycle intermediates and reduced glucose consumption, indicating that glycolysis is inhibited. Expression analyses revealed that D-glucal suppressed the expression of AF biosynthetic genes but promoted the expression of kojic acid biosynthetic genes.
  
  
  CONCLUSIONS
  D-glucal as a non-metabolizable glucose analog inhibits the AF biosynthesis pathway by suppressing the expression of AF biosynthetic genes. The inhibition may occur either directly through interfering with glycolysis, or indirectly through reduced oxidative stresses from kojic acid biosynthesis.
authors.forename: Jin-Dan
authors.initials: JD
authors.lastname: Zhang
authors.forename: Lida
authors.initials: L
authors.lastname: Han
authors.forename: Shijuan
authors.initials: S
authors.lastname: Yan
authors.affiliation: Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Nanxincun 20, Beijing 100093, China. cmliu@ibcas.ac.cn.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Liu
mesh_terms: D000348:Aflatoxins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D001231:Aspergillus flavus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D020869:Gene Expression Profiling; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D011753:Pyrones / Q000378:metabolism*
chemical_list: D000348:Aflatoxins; D003470:Culture Media; D011753:Pyrones; C001289:d-glucal; C011890:kojic acid; D003847:Deoxyglucose
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