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在乳酸脱氢酶缺陷的途径工程菌株中,透明质酸的产生和分子量增加。

Hyaluronan production and molecular weight is enhanced in pathway-engineered strains of lactate dehydrogenase-deficient .

作者信息

Kaur Mandeep, Jayaraman Guhan

机构信息

Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.

出版信息

Metab Eng Commun. 2016 Jan 22;3:15-23. doi: 10.1016/j.meteno.2016.01.003. eCollection 2016 Dec.

Abstract

The potential advantages of hyaluronic acid (HA) production by metabolically-engineered is constrained by the lower molecular weight and yield of HA obtained in these strains, compared to natural producers. Earlier studies have correlated lower HA yield with excessive lactate production in . cultures (Chauhan et al., 2014). In the present study, a three-fold increase was observed in the amount as well as molecular weight of HA produced by recombinant -mutant . strains. The diversion from lactate production in the -mutant strains resulted in excess ethanol and acetoin production and higher NAD/NADH ratio in these cultures. The initial NAD/NADH ratio showed a positive correlation with HA molecular weight as well as with the HA-precursor ratio (UDP-GlcUA/UDP-GlcNAc). The influence of NAD/NADH ratio on regulation of the concerned metabolic pathways was assessed by transcriptional analysis of key genes having putative binding sites of the NADH-binding transcriptional factor, Rex.

摘要

与天然生产者相比,通过代谢工程生产透明质酸(HA)的潜在优势受到这些菌株中获得的HA分子量较低和产量较低的限制。早期研究将较低的HA产量与培养物中过量的乳酸产生相关联(Chauhan等人,2014年)。在本研究中,观察到重组突变菌株产生的HA量和分子量增加了三倍。突变菌株中乳酸产生的转移导致这些培养物中过量的乙醇和乙偶姻产生以及更高的NAD/NADH比率。初始NAD/NADH比率与HA分子量以及HA前体比率(UDP-GlcUA/UDP-GlcNAc)呈正相关。通过对具有NADH结合转录因子Rex推定结合位点的关键基因进行转录分析,评估了NAD/NADH比率对相关代谢途径调控的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c01/5779726/1cc8caf398f4/gr1.jpg

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