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Peroxisomes Are Required for Efficient Penicillin Biosynthesis in Penicillium Chrysogenum

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Date 2010 Jul 6
PMID 20601503
Citations 41
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Abstract

In the fungus Penicillium chrysogenum, penicillin (PEN) production is compartmentalized in the cytosol and in peroxisomes. Here we show that intact peroxisomes that contain the two final enzymes of PEN biosynthesis, acyl coenzyme A (CoA):6-amino penicillanic acid acyltransferase (AT) as well as the side-chain precursor activation enzyme phenylacetyl CoA ligase (PCL), are crucial for efficient PEN synthesis. Moreover, increasing PEN titers are associated with increasing peroxisome numbers. However, not all conditions that result in enhanced peroxisome numbers simultaneously stimulate PEN production. We find that conditions that lead to peroxisome proliferation but simultaneously interfere with the normal physiology of the cell may be detrimental to antibiotic production. We furthermore show that peroxisomes develop in germinating conidiospores from reticule-like structures. During subsequent hyphal growth, peroxisome proliferation occurs at the tip of the growing hyphae, after which the organelles are distributed over newly formed subapical cells. We observed that the organelle proliferation machinery requires the dynamin-like protein Dnm1.

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References
1.
Thykaer J, Nielsen J . Metabolic engineering of beta-lactam production. Metab Eng. 2003; 5(1):56-69. DOI: 10.1016/s1096-7176(03)00003-x. View

2.
Liu F, Ng S, Lu Y, Low W, Lai J, Jedd G . Making two organelles from one: Woronin body biogenesis by peroxisomal protein sorting. J Cell Biol. 2008; 180(2):325-39. PMC: 2213590. DOI: 10.1083/jcb.200705049. View

3.
Gidijala L, Kiel J, Douma R, Seifar R, van Gulik W, Bovenberg R . An engineered yeast efficiently secreting penicillin. PLoS One. 2009; 4(12):e8317. PMC: 2789386. DOI: 10.1371/journal.pone.0008317. View

4.
van der Lende T, van de Kamp M, Berg M, Sjollema K, Bovenberg R, Veenhuis M . delta-(L-alpha-Aminoadipyl)-L-cysteinyl-D-valine synthetase, that mediates the first committed step in penicillin biosynthesis, is a cytosolic enzyme. Fungal Genet Biol. 2002; 37(1):49-55. DOI: 10.1016/s1087-1845(02)00036-1. View

5.
De Lucas J, Valenciano S, Dominguez A, Turner G, Laborda F . Characterization of oleate-nonutilizing mutants of Aspergillus nidulans isolated by the 3-amino-1,2,4-triazole positive selection method. Arch Microbiol. 1998; 168(6):504-12. DOI: 10.1007/s002030050528. View