Engineered biosynthesis of pimaricin derivatives with improved antifungal activity and reduced cytotoxicity
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| 024 | 7 | 0 | |a 10.1007/s00253-015-6635-9 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00253-015-6635-9 | ||
| 245 | 0 | 0 | |a Engineered biosynthesis of pimaricin derivatives with improved antifungal activity and reduced cytotoxicity |h [Elektronische Daten] |c [Zhen Qi, Qianjin Kang, Chunyan Jiang, Mo Han, Linquan Bai] |
| 520 | 3 | |a Pimaricin is an important antifungal antibiotic for antifungal therapy and prevention of mould contamination in the food industry. In this study, three new pimaricin derivatives, 12-decarboxy-12-methyl pimaricin (1), 4,5-desepoxy-12-decarboxy-12-methyl pimaricin (2), and 2-hydro-3-hydroxy-4,5-desepoxy-12-decarboxy-12-methyl pimaricin (3), were generated through the inactivation of P450 monooxygenase gene scnG in Streptomyces chattanoogensis L10. Compared with pimaricin, 1 displayed a twofold increase in antifungal activity against Candida albicans ATCC 14053 and a 4.5-fold decrease in cytotoxicity with erythrocytes, and 2 had comparable antifungal activity and reduced cytotoxicity, whereas 3 showed nearly no antifungal and hemolytic activities. Genetic and biochemical analyses proved that 1 is converted from 2 by P450 monooxygenase ScnD. Therefore, the overexpression of scnD in scnG-null strain eliminated the accumulation of 2 and improved the yield of 1 by 20%. Conversely, scnG/scnD double mutation abolished the production of 1 and improved the yield of 2 to 2.3-fold. These results indicate that the pimaricin derivatives with improved pharmacological properties obtained by genetic engineering can be further developed into antifungal agents for potential clinical application. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Streptomyces |2 nationallicence | |
| 690 | 7 | |a Polyene macrolide |2 nationallicence | |
| 690 | 7 | |a Pimaricin |2 nationallicence | |
| 690 | 7 | |a Antifungal activity |2 nationallicence | |
| 690 | 7 | |a Cytotoxicity |2 nationallicence | |
| 700 | 1 | |a Qi |D Zhen |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | |
| 700 | 1 | |a Kang |D Qianjin |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | |
| 700 | 1 | |a Jiang |D Chunyan |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | |
| 700 | 1 | |a Han |D Mo |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | |
| 700 | 1 | |a Bai |D Linquan |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | |
| 773 | 0 | |t Applied Microbiology and Biotechnology |d Springer Berlin Heidelberg |g 99/16(2015-08-01), 6745-6752 |x 0175-7598 |q 99:16<6745 |1 2015 |2 99 |o 253 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00253-015-6635-9 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00253-015-6635-9 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Qi |D Zhen |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kang |D Qianjin |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Jiang |D Chunyan |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Han |D Mo |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bai |D Linquan |u State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Applied Microbiology and Biotechnology |d Springer Berlin Heidelberg |g 99/16(2015-08-01), 6745-6752 |x 0175-7598 |q 99:16<6745 |1 2015 |2 99 |o 253 | ||