Key role of LaeA and velvet complex proteins on expression of β-lactam and PR-toxin genes in Penicillium chrysogenum: cross-talk regulation of secondary metabolite pathways.

摘要: Penicillium chrysogenum is an excellent model fungus to study the molecular mechanisms of control expression secondary metabolite genes. A key global regulator biosynthesis metabolites LaeA protein that interacts with other components velvet complex (VelA, VelB, VelC, VosA). These interact and regulate penicillin PR-toxin biosynthetic genes in P. chrysogenum. Both VelA are positive regulators biosynthesis, whereas VelB acts as antagonist effect VelA. Silencing or deletion laeA gene has a strong negative on overexpression increases production. Expression enhanced by autoinducers 1,3 diaminopropane spermidine. The cluster very poorly expressed under penicillin-production conditions (i.e. it near-silent cluster). Interestingly, downregulation high producing strain DS17690 was associated mutations both velA Analysis encoding this revealed acquired important during improvement programs thus altering ratio different (e.g. pigments, PR-toxin) synthesized mutants when compared parental wild type strain. Cross-talk pathways also been found various spp.: lacking produce increasing amounts PR-toxin, roqueforti silenced large mycophenolic acid. LaeA-velvet mediated regulation pathway cross-talk phenomenon great relevance for improving production novel metabolites, particularly those which produced trace encoded silent clusters.