title: Growth-Phase Sterigmatocystin Formation on Lactose Is Mediated via Low Specific Growth Rates in Aspergillus nidulans.
abstract: Seed contamination with polyketide mycotoxins such as sterigmatocystin (ST) produced byAspergilliis a worldwide issue. The ST biosynthetic pathway is well-characterized inA. nidulans, but regulatory aspects related to the carbon source are still enigmatic. This is particularly true for lactose, inasmuch as some ST production mutant strains still synthesize ST on lactose but not on other carbon substrates. Here, kinetic data revealed that on d-glucose, ST forms only after the sugar is depleted from the medium, while on lactose, ST appears when most of the carbon source is still available. Biomass-specified ST production on lactose was significantly higher than on d-glucose, suggesting that ST formation may either be mediated by a carbon catabolite regulatory mechanism, or induced by low specific growth rates attainable on lactose. These hypotheses were tested by d-glucose limited chemostat-type continuous fermentations. No ST formed at a high growth rate, while a low growth rate led to the formation of 0.4 mg·L-1ST. Similar results were obtained with a CreA mutant strain. We concluded that low specific growth rates may be the primary cause of mid-growth ST formation on lactose inA. nidulans, and that carbon utilization rates likely play a general regulatory role during biosynthesis.
authors.affiliation: Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary. nemeth.zoltan@science.unideb.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Németh
authors.affiliation: Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary. akos.molnar@science.unideb.hu.
authors.forename: Ákos P
authors.initials: ÁP
authors.lastname: Molnár
authors.affiliation: Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary. fejes.balazs91@gmail.com.
authors.forename: Balázs
authors.initials: B
authors.lastname: Fejes
authors.affiliation: Department of Physical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary. novak.levente@science.unideb.hu.
authors.forename: Levente
authors.initials: L
authors.lastname: Novák
authors.affiliation: Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary. karaffa.levente@science.unideb.hu.
authors.forename: Levente
authors.initials: L
authors.lastname: Karaffa
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA. npkeller@wisc.edu.|Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. npkeller@wisc.edu.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
authors.affiliation: Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary. kicsizsoka@yahoo.com.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Fekete
mesh_terms: D001233:Aspergillus nidulans / Q000254:growth & development / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007785:Lactose / Q000378:metabolism*; D013241:Sterigmatocystin / Q000096:biosynthesis*
chemical_list: D013241:Sterigmatocystin; D005947:Glucose; D007785:Lactose
keywords: ">d-glucose; Aspergillus nidulans; CreA; growth rate; lactose; sterigmatocystin