ELSEVIER FEMS Microbiology Letters 126 (1995) 63-68 Carbon regulation of penicillin biosynthesis in Aspergillus nidulans: A minor effect of mutations in creB and creC Eduardo A. Espeso, Jo& M. Fernhndez-Cafih, Miguel A. Pefialva * Departamento de Microbiologia Molecular, Centro de Investigaciones BioGgicas de1 C.S.I.C., Velcizquez 144, 28006 Madrid, Spain Received 25 November 1994; revised 6 December 1994; accepted 6 December 1994 Abstract Transcription of the Aspergillus nidulans ipn4 gene is under carbon regulation. Loss-of-function mutations in creB or creC do not cause full derepression of ipnA transcript levels in sucrose-grown mycelia and do not elevate repressed penicillin levels, indicating that neither of these genes plays a major regulatory role in penicillin biosynthesis. However, these mutations reduce external pH acidification, accelerate sucrose degradation and result in extracellular accumulation of resulting D-glucose and D-fructose. These effects would explain the partial elevation of carbon-repressed ipnA transcript levels observed in strains carrying creB_ or creC- mutations. Keywords: Carbon regulation; Penicillin; Secondary metabolism; Aspergillus nidulans; Carbon catabolite repression 1. Introduction The penicillin biosynthetic pathway is a model pathway of secondary metabolism. In zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Aspergillus nidulans, the synthesis of these antibiotics is under C regulation [ll. The presence of high levels of favourable C sources, such as glucose or sucrose, prevents antibiotic biosynthesis. Consequently, the extracellular levels of penicillins are higher in cul- tures grown on either less favourable C sources (such as lactose) or on low, limiting levels of more favoured C sources (such as D-fructose at 0.1%) [l]. C regulation of the penicillin pathway negatively controls transcription of at least ipnA [1,2], the gene encoding isopenicillin N synthase [3], a key enzyme * Corresponding author. in the route. In this respect, C regulation of ipnA transcription is similar to carbon catabolite repres- sion of primary metabolism genes [4]. However, it is independent of CreA, the transcriptional repressor mediating carbon catabolite repression [5-81. The regulatory gene mediating C regulation of the peni- cillin pathway (and presumably of other pathways of secondary metabolism) has not yet been identified. Transcription of ipn4 (and penicillin biosynthe- sis) is controlled by PacC, a transcription factor mediating changes in gene expression in response to environmental pH [9,10]. ipnA is a typical alkaline- expressed gene, presumably because its transcription is activated by PacC through specific binding sites located in its promoter [lO,ll]. pH regulation over- rides C regulation, and high levels of penicillins (and of the ipn4 transcript) are synthesised in alkaline media even in the presence of sucrose, a highly repressing C source [ll]. As the use of repressing C 0378-1097/95/$09.50 0 1995 Federation of European Microbiological Societies. All rights reserved SSDI 0378.1097(94)00527-3 Downloaded from https://academic.oup.com/femsle/article-abstract/126/1/63/532033 by guest on 02 June 2020