A reporter gene analysis of penicillin biosynthesis gene expression in Penicillium chrysogenum and its regulation by nitrogen and glucose catabolite repression

Abstract

Vectors which possess a truncated niaD gene encoding nitrate reductase were developed to allow targeted gene integration during transformation of an niaD mutant Penicillium chrysogenum host. The Penicillium genes pcbC and penAB are immediately adjacent to each other and are divergently transcribed, with an intergenic control region serving as their promoters. Gene fusions were constructed with a reporter gene, uid4, which encodes 0-glucuronidase. The pcbC-penAB intergenic region was fused to the uidA gene in both orientations so that regulated expression of each structural gene could be investigated. These fusion genes were targeted to the chromosomal site of the niaD locus of P. chrysogenum, and their expression was examined under different growth conditions. The expression of each of these penicillin biosynthesis genes was found to be regulated by nitrogen repression, glucose repression, and growth stage control.

Power input effects on degeneration in prolonged penicillin chemostat cultures: A systems analysis at flux, residual glucose, metabolite, and transcript levels

“…Figure SD2 shows the relation between q PenG and C s,in and there seems a tendency that q PenG decreases at higher C s,in . Although previous investigations found that the repression of the penicillin gene clusters is only induced by the extracellular glucose concentration (Brakhage, ; Feng, Friedlin, & Marzluf, ; Gutiérrez et al, ; Litzka, Bergh, den Brulle, Steidl, & Brakhage, ; Martín, Casqueiro, Kosalková, & Marcos, ; Revilla, Ramos, López‐Nieto, Alvarez, & Martin, ), however, in current experiments, the degeneration at 600 RPM occurred at much lower and decreasing C s,out . Combing these results, we reason that the repression of penicillin genes might be also induced at higher intracellular glucose levels and/or higher glucose uptake rates.…”

Comparative performance of different scale‐down simulators of substrate gradients in Penicillium chrysogenum cultures: the need of a biological systems response analysis

“…In previous studies, it was found that the transcription of the penicillin gene cluster is repressed by extracellular glucose (Revilla et al, 1986;Feng et al, 1994;Brakhage, 1998;Guti errez et al, 1999;Litzka et al, 1999;Mart ın et al, 1999). Further, Wang et al (2017) observed that a very low C s may induce the expression of the high-affinity glucose transporter genes, and the related glucose sensing can trigger metabolic rearrangement, for example futile cycling, which leads to an extra ATP consumption and eventually results in the decrease of penicillin production.…”

Towards high‐siderophore‐content foods: optimisation of coprogen production in submerged cultures of Penicillium nalgiovense

“…On the other hand, minor changes in the fermentation conditions, e.g. supplementation of the fermentation medium with 0.25 g L −1 (NH 4 ) 2 SO 4 , which elicits nitrogen repression of βlactam production, 54 kept antibiotic production at a low level (<0.5 mg L −1 ). Considering possible future research in this field, further studies are definitely needed to map or exclude possible mycotoxin production by P. nalgiovense 55 -57 under these fermentation conditions.…”