Improvement of Aspergillus nidulans penicillin production by targeting AcvA to peroxisomes |
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| Affiliation: | 1. Fakultät Physik, Technische Universität Dortmund, 44221 Dortmund, Germany;2. Department of Physics, Guelph-Waterloo Physics Institute, University of Guelph, MacNaughton Building, Gordon Street, Guelph, Ontario, Canada N1G 2W1;1. Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA;2. Department of Medicine, University of Florida, Gainesville, FL, 32611, USA;1. State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China;2. Department of Chemical Science, Kim Hyong Jik University of Education, Pyongyang 999093, Democratic People’s Republic of Korea;3. College of Engineering, The University of Georgia, Athens, GA 30602, USA;1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China;2. Faculty of Applied Sciences, UCSI University, UCSI Heights, Cheras, 56000 Kuala Lumpur, Malaysia;3. Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China;4. State Key Laboratory of Food Science and Technology, Jiangnan University, WuXi 214122, China |
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| Abstract: | Aspergillus nidulans is able to synthesize penicillin and serves as a model to study the regulation of its biosynthesis. Only three enzymes are required to form the beta lactam ring tripeptide, which is comprised of l-cysteine, l-valine and l-aminoadipic acid. Whereas two enzymes, AcvA and IpnA localize to the cytoplasm, AatA resides in peroxisomes. Here, we tested a novel strategy to improve penicillin production, namely the change of the residence of the enzymes involved in the biosynthesis. We tested if targeting of AcvA or IpnA (or both) to peroxisomes would increase the penicillin yield. Indeed, AcvA peroxisomal targeting led to a 3.2-fold increase. In contrast, targeting IpnA to peroxisomes caused a complete loss of penicillin production. Overexpression of acvA, ipnA or aatA resulted in 1.4, 2.8 and 3.1-fold more penicillin, respectively in comparison to wildtype. Simultaneous overexpression of all three enzymes resulted even in 6-fold more penicillin. Combination of acvA peroxisomal targeting and overexpression of the gene led to 5-fold increase of the penicillin titer. At last, the number of peroxisomes was increased through overexpression of pexK. A strain with the double number of peroxisomes produced 2.3 times more penicillin. These results show that penicillin production can be triggered at several levels of regulation, one of which is the subcellular localization of the enzymes. |
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| Keywords: | Penicillin Peroxisomes AcvA AatA IpnA |
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