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| 1 | Interrogation of Streptomyces avermitilis for efficient production of avermectins显示文摘The 2015 Nobel Prize in Physiology or Medicine has been awarded to avermectins and artemisinin,respectively.Avermectins produced by Streptomyces avermitilis are excellent anthelmintic and potential antibiotic agents.Because wild-type strains only produce low levels of avermectins,much research effort has focused on improvements in avermectin production to meet the ever increasing demand for such compounds.This review describes the strategies that have been widely employed and the future prospects of synthetic biology applications in avermectin yield improvement.With the help of genome sequencing of S.avermitilis and an understanding of the avermectin biosynthetic/regulatory pathways,synthetic and systems biotechnology approaches have been applied for precision engineering.We focus on the design and synthesis of biological chassis,parts,devices,and modules from diverse microbes to reconstruct and optimize their dynamic processes,as well as predict favorable effective overproduction of avermectins by a 4Ms strategy(Mine,Model,Manipulation,and Measurement). | Jinsong Chen Mei Liu Xueting Liu Jin Miao Chengzhang Fu Heyong Gao Rolf Muller Qing Zhang Lixin Zhang | 2016 | Synthetic and Systems Biotechnology2016，1，1： | 10 |
| 2 | Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea显示文摘Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea;however,its biosynthetic cluster lacks a regulatory gene,limiting the yield enhancement via regulation engineering of S.erythraea.Herein,six TetR family transcriptional regulators(TFRs)belonging to three genomic context types were individually inactivated in S.erythraea A226,and one of them,SACE_3446,was proved to play a negative role in regulating erythromycin biosynthesis.EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI,the resistant gene ermE and the adjacent gene SACE_3447(encoding a longchain fatty-acid CoA ligase),and repressed their transcription.Furthermore,we explored the interaction relationships of SACE_3446 and previously identified TFRs(SACE_3986 and SACE_7301)associated with erythromycin production.Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis,we individually and concomitantly inactivated them in an industrial S.erythraea WB.Compared with WB,the WBΔ3446 and WBΔ3446Δ3986 mutants respectively displayed 36%and 65%yield enhancement of erythromycin A,following significantly elevated transcription of eryAI and ermE.When cultured in a 5 L fermentor,erythromycin A ofWBΔ3446 and WBΔ3446Δ3986 successively reached 4095 mg/L and 4670 mg/L with 23%and 41%production improvement relative to WB.The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete. | Hang Wu Yansheng Wang Li Yuan Yongrong Mao Weiwei Wang Lin Zhu Panpan Wu Chengzhang Fu Rolf Muller David T.Weaver Lixin Zhang Buchang Zhang | 2016 | Synthetic and Systems Biotechnology2016，1，1： | 7 |
| 3 | Heart-directed expression of a human cardiac isoform of cAMP-response element modulator in transgenic mice显示文摘 | Muller FU Lewin G Baba HA | 2005 | J Biol Chem2005，280，8： | 1 |
| 4 | In cardiomyocyte hypoxia, insulin-like growth factor- I -induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase - dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 5 | In car- diomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH- kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，： | 1 |
| 6 | In cardiomyocyte hypoxia, insulin-like growth factor-l-induced antiapoptotic signaling requires hosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 7 | In cardiomyocyte hypoxia, insulin-like growth factor-l-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase- dependent and mitogen- activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 8 | In cardiomyocyte hypoxia, in- sulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidyli- nositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，： | 1 |
| 9 | In cardiomyocyte hypoxia,insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding p显示文摘 | Mehrhof FB Muller FU Bergmann MW | | 0，，： | 1 |
| 10 | In cardiomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic sig- naling requires phosphatidylinositol - 3 - OH - kinase - dependent and mitogenactivated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 11 | In cardiomyocyte hypoxia, insulin-like growth factor-Ⅰ-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein显示文摘 | MEHRHOF FB MULLER FU BERGMANN MW | 2001 | Circulation2001，104，17： | 1 |
| 12 | In cardiomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 13 | In cardiomyocyte hypoxia,insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 14 | Total Cavopulmonary Connection:Lateral Tunnel Anastomosis or Extracardiac Conduit?——an Analysis of 114 Consecutive Patients显示文摘Objective To compare the postoperative outcomes of patients with the diagnostic univentricular heart undergoing lateral tunnel(LT) operation with extracardiac conduit(EC) operation.Methods From June 1996 to July 2007,114 consecutive patients with a single ventricle underwent total cavopulmonary connection(TCPC) in Children's Heart Center,University Hospital Giessen and Marburg GmbH,Germany.A LT was performed in 19(16.7%) patients,and an EC in 95(83.3%) patients.The mean age of EC group was 50.8±31.6(ranging from 22 to 212) months,and that of LT group was 61.5±41.2(ranging from 30 to 168) months.Early and midterm outcomes of two groups were analyzed.Results One died in LT group(5.3%) and three in EC group(3.2%).The overall mortality was 3.5%.There was no significant difference in mortality between EC and LT groups(P>0.05).The postoperative pulmonary arterial pressure,oxygen saturation,and effusion time of two groups had no significant difference(all P>0.05).No significant difference in the occurrences of complications(arrhythmias,enteropathy,and thrombosis) was found between two groups after operation(P>0.05).Conclusions There seems no difference between LT and EC in the clinical results in the early and middle postoperative stage.Glenn anastomosis followed by an EC seems to have some advantages. | Song Fu Klaus Valeske Matia Muller Dietmer Schranz Hakan Akinturk | 2009 | Chinese Medical Sciences Journal2009，24，2： | 1 |
| 15 | In cardiomyocyte hypoxia, insulin-like growth factor-induced antiapoptotic signaling requires phoshpatidylinnsitol-3-OH -kinase-dependenl and mitogen-actirated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein 显示文摘 | Mehrhof FB Muller FU Bergmann MW | 2001 | Circulation2001，104，17： | 1 |
| 16 | Oncogenic activation of the human trk proto-oncogene by recombination with the ribosomal large subunit protein L7a显示文摘 | Ziemiecki A Muller RG Fu XC | 1990 | EMBO J1990，9，1： | 1 |
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