title: A functional bikaverin biosynthesis gene cluster in rare strains of Botrytis cinerea is positively controlled by VELVET.
abstract: The gene cluster responsible for the biosynthesis of the red polyketidic pigment bikaverin has only been characterized in Fusarium ssp. so far. Recently, a highly homologous but incomplete and nonfunctional bikaverin cluster has been found in the genome of the unrelated phytopathogenic fungus Botrytis cinerea. In this study, we provided evidence that rare B. cinerea strains such as 1750 have a complete and functional cluster comprising the six genes orthologous to Fusarium fujikuroi ffbik1-ffbik6 and do produce bikaverin. Phylogenetic analysis confirmed that the whole cluster was acquired from Fusarium through a horizontal gene transfer (HGT). In the bikaverin-nonproducing strain B05.10, the genes encoding bikaverin biosynthesis enzymes are nonfunctional due to deleterious mutations (bcbik2-3) or missing (bcbik1) but interestingly, the genes encoding the regulatory proteins BcBIK4 and BcBIK5 do not harbor deleterious mutations which suggests that they may still be functional. Heterologous complementation of the F. fujikuroi Δffbik4 mutant confirmed that bcbik4 of strain B05.10 is indeed fully functional. Deletion of bcvel1 in the pink strain 1750 resulted in loss of bikaverin and overproduction of melanin indicating that the VELVET protein BcVEL1 regulates the biosynthesis of the two pigments in an opposite manner. Although strain 1750 itself expresses a truncated BcVEL1 protein (100 instead of 575 aa) that is nonfunctional with regard to sclerotia formation, virulence and oxalic acid formation, it is sufficient to regulate pigment biosynthesis (bikaverin and melanin) and fenhexamid HydR2 type of resistance. Finally, a genetic cross between strain 1750 and a bikaverin-nonproducing strain sensitive to fenhexamid revealed that the functional bikaverin cluster is genetically linked to the HydR2 locus.
authors: Institute for Biology and Biotechnology of Plants, Westfälische Wilhelms-University, Münster, Germany.
authors: Julia
authors: J
authors: Schumacher
authors: Angélique
authors: A
authors: Gautier
authors: Guillaume
authors: G
authors: Morgant
authors: Lena
authors: L
authors: Studt
authors: Paul-Henri
authors: PH
authors: Ducrot
authors: Pascal
authors: P
authors: Le Pêcheur
authors: Saad
authors: S
authors: Azeddine
authors: Sabine
authors: S
authors: Fillinger
authors: Pierre
authors: P
authors: Leroux
authors: Bettina
authors: B
authors: Tudzynski
authors: Muriel
authors: M
authors: Viaud
mesh_terms: D000577:Amides / Q000494:pharmacology; D020171:Botrytis / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000187:drug effects; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005670:Fusarium / Q000145:classification / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D022761:Gene Transfer, Horizontal; D005816:Genetic Complementation Test; D056426:Genetic Loci; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics; D005810:Multigene Family; D009154:Mutation; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D044004:Xanthones / Q000378:metabolism*
chemical_list: D000577:Amides; D005656:Fungal Proteins; D008543:Melanins; D014157:Transcription Factors; D044004:Xanthones; C000269:bikaverin; C451426:N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide