Expression of the cefG gene is limiting for cephalosporin biosynthesis in Acremonium chrysogenum

Applied Microbiology and Biotechnology
S GutiérrezJ F Martín

Abstract

The conversion of deacetylcephalosporin C to cephalosporin C is inefficient in most Acremonium chrysogenum strains. The cefG gene, which encodes deacetylcephalosporin C acetyltransferase, is expressed very poorly in A. chrysogenum as compared to other genes of the cephalosporin pathway. Introduction of additional copies of the cefG gene with its native promoter (in two different constructions with upstream regions of 1056 bp and 538 bp respectively) did not produce a significant increase of the steady-state level of the cefG transcript. Expression of the cefG gene from the promoters of (i) the glyceraldehyde-3-phosphate dehydrogenase (gpd) gene of Aspergillus nidulans, (ii) the glucoamylase (gla) gene of Aspergillus niger, (iii) the glutamate dehydrogenase (gdh) and (iv) the isopenicillin N synthase (pcbC) genes of Penicillium chrysogenum, led to very high steady-state levels of cefG transcript and to increased deacetylcephalosporin-C acetyltransferase protein concentration (as shown by immunoblotting) and enzyme activity in the transformants. Southern analysis showed that integration of the new constructions occurred at sites different from that of the endogenous cefG gene. Cephalosporin production was increased two- to threef...Continue Reading

Citations

Oct 12, 2012·Applied Microbiology and Biotechnology·Marta Fernández-AguadoJuan F Martín
Nov 22, 2002·Trends in Biotechnology·Juan F Martín, Arnold L Demain
May 17, 2003·Metabolic Engineering·Jette Thykaer, Jens Nielsen
Oct 14, 2011·Yi chuan = Hereditas·You-Jia Hu, Bao-Quan Zhu
Feb 1, 2014·Metabolic Engineering·M Fernández-AguadoR V Ullán
Feb 14, 2006·FEMS Microbiology Reviews·Jose L Adrio, Arnold L Demain
Nov 9, 2012·Natural Product Reports·Refaat B HamedChristopher J Schofield
Nov 19, 2015·Frontiers in Microbiology·Esclaudys PérezRosa Hermosa

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