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| 1 | Improvement of pristinamycin I(PI)production in Streptomyces pristinaespiralis by metabolic engineering approaches显示文摘Pristinamycin,produced by Streptomyces pristinaespiralis,which is a streptogramin-like antibiotic consisting of two chemically unrelated components:pristinamycin I(PI)and pristinamycin II(PII),shows potent activity against many antibiotic-resistant pathogens.However,so far pristinamycin production titers are still quite low,particularly those of PI.In this study,we constructed a PI single component producing strain by deleting the PII biosynthetic genes(snaE1 and snaE2).Then,two metabolic engineering approaches,including deletion of the repressor gene papR3 and chromosomal integration of an extra copy of the PI biosynthetic gene cluster(BGC),were employed to improve PI production.The final engineered strain DPIIDpapR3/PI produced a maximum PI level of 132 mg/L,with an approximately 2.4-fold higher than that of the parental strain S.pristinaespiralis HCCB10218.Considering that the PI biosynthetic genes are clustered in two main regions in the 210 kb“supercluster”containing the PI and PII biosynthetic genes as well as a cryptic polyketide BGC,these two regions were cloned separately and then were successfully assembled into the PI BGC by the transformation-associated recombination(TAR)system.Collectively,the metabolic engineering approaches employed is very efficient for strain improvement in order to enhance PI titer. | Jiali Meng Rongrong Feng Guosong Zheng Mei Ge Yvonne Mast Wolfgang Wohlleben Jufang Gao Weihong Jiang Yinhua Lu | 2017 | Synthetic and Systems Biotechnology2017，2，2： | 7 |
| 2 | Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production显示文摘The isoprenoid brasilicardin A is a promising immunosuppressant compound with a unique mode of action,high potency and reduced toxicity compared to today's standard drugs.However,production of brasilicardin has been hampered since the producer strain Nocardia terpenica IFM0406 synthesizes brasilicardin in only low amounts and is a biosafety level 2 organism.Previously,we were able to heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis japonicum.Four brasilicardin congeners,intermediates of the BraA biosynthesis,were produced.Since chemical synthesis of the brasilicardin core structure has remained elusive we intended to produce high amounts of the brasilicardin backbone for semi synthesis and derivatization.Therefore,we used a metabolic engineering approach to increase heterologous production of brasilicardin in A.japonicum.Simultaneous heterologous expression of genes encoding the MVA pathway and expression of diterpenoid specific prenyltransferases were used to increase the provision of the isoprenoid precursor isopentenyl diphosphate(IPP)and to channel the precursor into the direction of diterpenoid biosynthesis.Both approaches contributed to an elevated heterologous production of the brasilicardin backbone,which can now be used as a starting point for semi synthesis of new brasilicardin congeners with better properties. | Paul N.Schwarz Luisa Roller Andreas Kulik Wolfgang Wohlleben Evi Stegmann | 2018 | Synthetic and Systems Biotechnology2018，3，1： | 3 |
| 3 | Short term inhalation toxicity of a liquid aerosol of CdS/Cd (O1-1)2 core shell quantum dots in male Wistar rats显示文摘 | MA-HOCK L BRILL S WOHLLEBEN W | 2012 | Toxicology Letters2012，208，2： | 1 |
| 4 | Insulin-like growth factor-1 contributes to neovasculafization in age-related macular degeneration 显示文摘 | Rosenthal R Wohlleben H Malek G | 2004 | Biochem Biophys Res Commun2004，323，4： | 1 |
| 5 | Recent changes in the exchange of sea ice between the Arctic Ocean and the Canadian Arctic Archi- pelago显示文摘 | Howell S E L Wohlleben T Dabboor M | 2013 | Journal of Geophysical Research:Oceans2013，118，7： | 1 |
| 6 | Nucleotide sequence of the PhosphinothricinN-acetyltransferase gene from the Streptomyces hygroscopicus Tu 494 and its expression inNicotiana tobacum显示文摘 | WOHLLEBEN W AMOLD W BROER I, | 1988 | Gene1988，70，： | 1 |
| 7 | Sea-ice motion and flux within the Prince Gustaf Adolf Sea,Queen Elizabeth Islands,Canada during 2010显示文摘 | Wohlleben T Howell S E L Komarov T A A | 2012 | Atmosphere Ocean2012，51，1： | 1 |
| 8 | Helminth derived products inhibit the develop-ment of allergic responses in mice显示文摘 | Trujillo-Vargas CM Werner-Klein M Wohlleben G | 2007 | Am J Respir CritCare Med2007，175，33： | 1 |
| 9 | Analysis of maturation states of rat bone marrow-derived dendritic cells using an improved culture technique显示文摘 | Grauer O Wohlleben G Seubert S | 2002 | Histochem Cell Biol2002，117，4： | 1 |
| 10 | Helminth infection modulates the development of allergen-induced airway inflammation显示文摘 | Wohlleben G Trujillo C Muller J | 2004 | Int Immunol2004，16，4： | 1 |
| 11 | Shear and elongational flow behavior of acrylic thickener solutions Part I : Effect of intermolecular aggregation显示文摘 | Saeid Kheirandish llshat Guybaidullin Wende Wohlleben | 2008 | Rheol Acta2008，47，： | 1 |
| 12 | Helminth-derived products inhibit the development of allergic responses in mice显示文摘 | Trujillo-Vargas CM Werner-Klein M Wohlleben G | 2007 | AM Respir Crit Care Med2007，175，4： | 1 |
| 13 | Helminth-derived products inhibit the development of allergic responses in mice显示文摘 | Trujillo-Vargas C M Werner-Klein M Wohlleben G Polte T Hansen G Ehlers S | 2007 | Am J Respir Crit Care Med2007，175，： | 1 |
| 14 | Vortex Formation in a Stirred Bose-Einstein condensate显示文摘 | MADISON K W CHEVY F WOHLLEBEN W | 2000 | Phys Rev Lett2000，84，5： | 1 |
| 15 | Analysis of maturation states of rat bone marrow-derived dendritic cells using an improved culture technique显示文摘 | Grauer O Wohlleben G Seubert S | 2002 | Histochem Cell Biol2002，117，4： | 1 |
| 16 | Quantum Control of Energy Flow in Light Harvesting 显示文摘 | Herek J L Wohlleben W Cogdell R J | 2002 | Nature2002，417，： | 1 |
| 17 | Infection with influenza A virus leads to flu antigen-induced cutaneous anaphylaxis in mice 显示文摘 | Grunewald SM Hahn C Wohlleben G | 2002 | J Invest Dermatol2002，118，： | 1 |
| 18 | Ana lysis of maturation states of rat bone marrow-derived dendritic cells using an improved culture technique 显示文摘 | GRAUER O WOHLLEBEN G SEUBERT S | 2002 | Histochem Cell Biol2002，117，： | 1 |
| 19 | Analysis of maturation states of rat bone marrow-derived dendritic cells using and improved cultrue technique显示文摘 | Grauer O Wohlleben G Seubert S | 2002 | Histochem Cell Biol2002，117，4： | 1 |
| 20 | Realization of a time-domain Fresnel lens with coherent control 显示文摘 | Wendel Wohlleben Beatrice Chatel | 2002 | Physical Review Letter2002，89，20： | 1 |
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