TRENDS IN BIOTECHNOLOGY
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2025
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IF 14.9
Panpan Wu,Zhenyue Xu,Zhongqiu Meng,Ketao Chen,Hao Lin,Min Zhang,Lixin Zhang,Buchang Zhang,Hang Wu
Nicotinamide adenine dinucleotide (NAD) homeostasis is crucial for secondary metabolism in antibiotic-producing actinomycetes. However, NAD-based dynamic control strategies for boosting antibiotic titers have not been reported. We identified SACE_1905, an alcohol dehydrogenase in Saccharopolyspora erythraea , which converts NADH to NAD + . Overexpressing SACE_1905 lowered the cellular NADH/NAD + ratio, facilitating carbon source utilization and erythromycin biosynthetic precursor supply, concurrently improving cell growth and erythromycin yield. To balance primary and secondary metabolism, we developed a strategy that fine-tunes SACE_1905 expression with inducible clustered regularly interspaced short palindromic repeat interference (CRISPRi) to dynamically modulate the NADH/NAD + ratio, which we named diNAD. Optimized diNAD redirected carbon flux, maximizing erythromycin biosynthesis at a moderate NADH/NAD + ratio during the stationary phase. Based on its utility in actinorhodin and avermectin overproduction in Streptomyces coelicolor and Streptomyces avermitilis , we show that diNAD is effective in augmenting antibiotic titers in actinomycetes.
研究领域:
微生物学
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生物技术
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合成生物学
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生物工程
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分子生物学
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DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
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2024
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IF 3.7
Xilin Huang,Xuli Gao,Junbao Huang,Yani Luo,Wei Tao,Mingyu Guo,Yongyuan Liu,Jing Wu,Yu Chen,Yan Liu
A recombinant strain (BS168-Δ bdhA ) that increased co-production of MK-7 and NK was constructed by knocking out the 2,3-butanediol dehydrogenase gene ( bdhA ) of Bacillus subtilis 168 to reduce the carbon spillover. The results showed that the 2,3- butanediol content in the recombinant strain was reduced by 64% to 2.76 g/L. The recombinant strain had an MK-7 production of 30.6 mg/L and an NK activity of 6.5 FU/mL. RNA-Seq analysis showed that: bdhA knockdown blocked the carbon flux of 2,3-butanediol and promoted glycerol uptake, and the carbon flux flowed more to the MK-7 and NK synthesis pathways. The negative regulator of NK, codY , was down-regulated by 2.19-fold. secA , which is responsible for the energy supply of transmembrane proteins, was down-regulated by 0.37-fold, the Tat secretion pathway was up-regulated by 2.8-fold and 0.5-fold for tatAD and tatC , respectively. This study revealed the mechanism of co-production of MK-7 and NK in recombinant strains for the first time and revealed potential molecular targets to promote the co-production of MK-7 and NK, which will provide a new strategy for metabolic engineering to increase the production of MK-7 and NK.
研究领域:
微生物学
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分子生物学
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代谢工程
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DOI
高影响因子
Frontiers in Microbiology
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2020
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IF 4.236
Wang Xiaoshuai,Chen Lei,Liu Jing,Sun Tao,Zhang Weiwen
myo-inositol (MI) is an essential growth factor, nutritional source, and important precursor for many derivatives like D-chiro-inositol. In this study, attempts were made to achieve the “green biosynthesis” of MI in a model photosynthetic cyanobacterium Synechocystis sp. PCC 6803. First, several genes encoding myo-inositol-1-phosphate synthases and myo-inositol-1-monophosphatase, catalyzing the first or the second step of MI synthesis, were introduced, respectively, into Synechocystis. The results showed that the engineered strain carrying myo-inositol-1-phosphate synthase gene from Saccharomyces cerevisiae was able to produce MI at 0.97 mg L–1. Second, the combined overexpression of genes related to the two catalyzing processes increased the production up to 1.42 mg L–1. Third, to re-direct more cellular carbon flux into MI synthesis, an inducible small RNA regulatory tool, based on MicC-Hfq, was utilized to control the competing pathways of MI biosynthesis, resulting in MI production of ∼7.93 mg L–1. Finally, by optimizing the cultivation condition via supplying bicarbonate to enhance carbon fixation, a final MI production up to 12.72 mg L–1 was achieved, representing a ∼12-fold increase compared with the initial MI-producing strain. This study provides a light-driven green synthetic strategy for MI directly from CO2 in cyanobacterial chassis and represents a renewable alternative that may deserve further optimization in the future.
研究领域:
微生物学
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生物技术
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合成生物学
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DOI
PubMed
高影响因子
CARBON
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2023
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IF 10.9
Qianru Wu,Xuan Lv,Ningning Xu,Liantao Xin,Guangyi Lin,Kezheng Chen,Maoshuai He
Plastic waste has posed an ever-growing environmental threat to the United Nations’ sustainable development goals. Converting plastic polymers into high value chemicals like carbon nanotubes is a promising approach for recycling without carbon dioxide emission. Using a two-stage pyrolysis-catalytic reactor, we herein report the transformation of five types of plastic polymers into high-quality single-walled carbon nanotubes (SWNTs) with the assistance of a rationally designed heterogeneous catalyst , i.e., an iron metal catalyst supported by porous magnesia . Because of the high metal dispersion and the large carbon solubility of the active component, the heterogeneous catalyst affords the formation of uniform metal particles which can sustain high carbon fluxes, resulting in the synthesis of high quality SWNTs. More importantly, the approach is also demonstrated with mixtures of plastic polymers. This work helps gain deep insights into the mechanisms of plastic polymer conversion to SWNTs, accelerating the progress toward a sustainable plastic economy.
研究领域:
材料科学
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环境科学
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化学工程
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可持续性
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）