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| Articles
by
Wei Deng |
Total Records (
3 ) for
Wei Deng |
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Yun Chen
,
Wei Deng
,
Jiequn Wu
,
Jiangchao Qian
,
Ju Chu
,
Yingping Zhuang
,
Siliang Zhang
and
Wen Liu
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Erythromycin A (Er-A) is the most potent and clinically important member in the Er family produced by Saccharopolyspora erythraea. Er-B and Er-C, which are biologically much less active and cause greater side effects than Er-A, serve as the intermediates for Er-A biosynthesis and impurities in fermentation processes of many industrial strains. In this study, systematical modulation of the amounts of tailoring enzymes EryK (a P450 hydroxylase) and EryG (an S-adenosylmethionine-dependent O-methyltransferase) was carried out by genetic engineering in S. erythraea, including alterations of gene copy number ratio and organization and integrating the locus on the chromosome by homologous recombination. Introduction of additional eryK and eryG genes into S. erythraea showed significant impacts on their transcription levels and enhanced the biotransformation process from Er-D to Er-A with gene dose effects. At the eryK/eryG copy number ratio of 3:2 as well as their resultant transcript ratio of around 2.5:1 to 3.0:1, Er-B and Er-C were nearly completely eliminated and accordingly converted to Er-A, and the Er titer was improved by around 25% in the recombinant strain ZL1004 (genotype PermK*-K-K-G + PermE*-K + PermA*-G) and ZL1007 (genotype PermK*-K-G-K + PermE*-K + PermA*-G). This study may contribute to the continuous efforts toward further evaluation of the Er-producing system, with the aims of improving Er-A purity and production at the fermentation stage and lowering the production costs and environmental concerns in industry. |
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Lei Li
,
Wei Deng
,
Jie Song
,
Wei Ding
,
Qun- Fei Zhao
,
Chao Peng
,
Wei- Wen Song
,
Gong -Li Tang
and
Wen Liu
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Saframycin A (SFM-A), produced by Streptomyces lavendulae NRRL 11002, belongs to the tetrahydroisoquinoline family of antibiotics, and its core is structurally similar to the core of ecteinascidin 743, which is a highly potent antitumor drug isolated from a marine tunicate. In this study, the biosynthetic gene cluster for SFM-A was cloned and localized to a 62-kb contiguous DNA region. Sequence analysis revealed 30 genes that constitute the SFM-A gene cluster, encoding an unusual nonribosomal peptide synthetase (NRPS) system and tailoring enzymes and regulatory and resistance proteins. The results of substrate prediction and in vitro characterization of the adenylation specificities of this NRPS system support the hypothesis that the last module acts in an iterative manner to form a tetrapeptidyl intermediate and that the colinearity rule does not apply. Although this mechanism is different from those proposed for the SFM-A analogs SFM-Mx1 and safracin B (SAC-B), based on the high similarity of these systems, it is likely they share a common mechanism of biosynthesis as we describe here. Construction of the biosynthetic pathway of SFM-Y3, an aminated SFM-A, was achieved in the SAC-B producer (Pseudomonas fluorescens). These findings not only shed new insight on tetrahydroisoquinoline biosynthesis but also demonstrate the feasibility of engineering microorganisms to generate structurally more complex and biologically more active analogs by combinatorial biosynthesis. |
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Wei Deng
,
Min-Hui Li
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Xiaogong Wang
and
Patrick Keller
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The pioneering work of Professor de Gennes in the field of liquid crystalline polymers and elastomers is outlined with an emphasis on artificial muscles. To illustrate the presentation, results on light-responsive nematic liquid crystalline elastomer fibres are reported. Two kinds of light-responsive wires were fabricated from an azobenzene-containing liquid crystalline copolymer with, or without cross-linking. Cross-linked wires were obtained by the reaction between the hydroxyl groups of the liquid crystalline copolymer and the diisocyanate groups of the cross-linker. The wires showed light-responsive bending towards the direction of the incident UV light at room temperature. Uncross-linked wires, drawn from the pure azobenzene copolymer, presented the same UV light-induced bending properties. |
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