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Metabolic engineering using acetate as a promising building block for the production of bio‐based chemicals 利用乙酸盐作为生产生物基化学品的有前景的构建块的代谢工程
Pub Date : 2022-12-01 DOI: 10.1016/j.engmic.2022.100036
Guiping Gong , Bo Wu , Linpei Liu, Jianting Li, Qili Zhu, Mingxiong He, Guoquan Hu

The production of biofuels and biochemicals derived from microbial fermentation has received a lot of attention and interest in light of concerns about the depletion of fossil fuel resources and climatic degeneration. However, the economic viability of feedstocks for biological conversion remains a barrier, urging researchers to develop renewable and sustainable low-cost carbon sources for future bioindustries. Owing to the numerous advantages, acetate has been regarded as a promising feedstock targeting the production of acetyl-CoA-derived chemicals. This review aims to highlight the potential of acetate as a building block in industrial biotechnology for the production of bio-based chemicals with metabolic engineering. Different alternative approaches and routes comprised of lignocellulosic biomass, waste streams, and C1 gas for acetate generation are briefly described and evaluated. Then, a thorough explanation of the metabolic pathway for biotechnological acetate conversion, cellular transport, and toxin tolerance is described. Particularly, current developments in metabolic engineering of the manufacture of biochemicals from acetate are summarized in detail, with various microbial cell factories and strategies proposed to improve acetate assimilation and enhance product formation. Challenges and future development for acetate generation and assimilation as well as chemicals production from acetate is eventually shown. This review provides an overview of the current status of acetate utilization and proves the great potential of acetate with metabolic engineering in industrial biotechnology.

鉴于人们对化石燃料资源枯竭和气候退化的担忧,从微生物发酵中提取的生物燃料和生物化学品的生产受到了很多关注和兴趣。然而,生物转化原料的经济可行性仍然是一个障碍,敦促研究人员为未来的生物工业开发可再生和可持续的低成本碳源。由于具有许多优点,乙酸盐被认为是一种很有前途的原料,用于生产乙酰辅酶a衍生的化学品。这篇综述旨在强调乙酸盐作为工业生物技术中利用代谢工程生产生物基化学品的构建块的潜力。简要描述和评估了由木质纤维素生物质、废物流和C1气体组成的用于乙酸盐生成的不同替代方法和路线。然后,对生物技术醋酸盐转化、细胞转运和毒素耐受的代谢途径进行了全面的解释。特别是,详细总结了由乙酸盐生产生物化学品的代谢工程的最新进展,提出了各种微生物细胞工厂和策略,以改善乙酸盐的同化和促进产物的形成。最终展示了乙酸盐生成和同化以及乙酸盐生产化学品的挑战和未来发展。这篇综述综述了乙酸盐的利用现状,并证明了乙酸盐与代谢工程在工业生物技术中的巨大潜力。
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引用次数: 14
Lysine acetylation decreases enzyme activity and protein level of Escherichia coli lactate dehydrogenase 赖氨酸乙酰化降低大肠杆菌乳酸脱氢酶的酶活性和蛋白质水平
Pub Date : 2022-12-01 DOI: 10.1016/j.engmic.2022.100045
Min Liu , Meitong Huo , Likun Guo , Yingxin Fu , Mo Xian , Qingsheng Qi , Wei Liu , Guang Zhao

Lactate is an important bulk chemical with widespread applications and a major byproduct of other chemicals bioprocess in microbial fermentation. Lactate dehydrogenase A (LdhA) catalyzes the synthesis of lactate from pyruvate. Lysine acetylation is an evolutionarily conserved post-translational modification; however, the mechanisms underlying the regulation of LdhA function by lysine acetylation in Escherichia coli remain poorly understood. Herein, we demonstrate acetylation of E. coli LdhA occurs via enzymatic and non-enzymatic mechanisms. Further, we show carbon source type and concentration affect the lysine acetylation status of LdhA via a non-enzymatic mechanism. Lysine acetylation significantly inhibits the enzymatic activity and protein level of LdhA. The results of the present study demonstrate lysine acetylation of E. coli LdhA is irreversible. Understanding of the effects of lysine acetylation on LdhA function may provide a new perspective for regulating lactate production in microbial synthesis.

乳酸是一种应用广泛的重要大宗化学品,也是微生物发酵中其他化学品生物过程的主要副产品。乳酸脱氢酶A(LdhA)催化丙酮酸盐合成乳酸。赖氨酸乙酰化是一种进化上保守的翻译后修饰;然而,赖氨酸乙酰化在大肠杆菌中调节LdhA功能的机制仍知之甚少。在此,我们证明了大肠杆菌LdhA的乙酰化是通过酶和非酶机制发生的。此外,我们发现碳源类型和浓度通过非酶机制影响LdhA的赖氨酸乙酰化状态。赖氨酸乙酰化显著抑制LdhA的酶活性和蛋白质水平。本研究结果表明大肠杆菌LdhA的赖氨酸乙酰化是不可逆的。了解赖氨酸乙酰化对LdhA功能的影响可能为调节微生物合成中乳酸的产生提供新的视角。
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引用次数: 0
Bioproduction of monoterpene indole alkaloids in a single cell factory 单细胞工厂中单萜吲哚生物碱的生物生产
Pub Date : 2022-12-01 DOI: 10.1016/j.engmic.2022.100050
Jianping Huang , Shengxiong Huang

The de novo biosynthesis of vindoline and catharanthine, the direct precursors used for industrial production of the anti-cancer drug vinblastine, has been achieved in the yeast cell factory. To date, this is the longest natural product biosynthesis pathway that has been successfully transferred from plants to microorganisms, indicating the possibility of producing more than 3,000 other monoterpene indole alkaloids in yeast by synthetic genome engineering.

长春花碱和长春花碱是抗癌药物长春花碱工业生产的直接前体,它们的从头生物合成已在酵母细胞工厂中实现。到目前为止,这是从植物成功转移到微生物的最长的天然产物生物合成途径,表明通过合成基因组工程在酵母中生产3000多种其他单萜吲哚生物碱的可能性。
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引用次数: 3
Cascade-Cas3 facilitates high-accuracy genome engineering in Pseudomonas using phage-encoded homologous recombination Cascade-Cas3利用噬菌体编码的同源重组促进假单胞菌的高精度基因组工程
Pub Date : 2022-12-01 DOI: 10.1016/j.engmic.2022.100046
Wentao Zheng , Yandong Xia , Xue Wang , Shiqing Gao , Diao Zhou , Jun Fu , Ruijuan Li , Jia Yin

Phage-encoded homologous recombination (PEHR) is an efficient tool for bacterial genome editing. We previously developed and utilized a Pseudomonas-specific PEHR system. However, when using the PEHR system for Pseudomonas genome editing, false positives can be a problem. In this study, we combined a compact Cascade-Cas3 system from P. aeruginosa (PaeCas3c) with a Pseudomonas-specific PEHR system, and the results of our recombineering assay showed that this compact Cascade-Cas3 system can significantly improve PEHR recombineering accuracy.

噬菌体编码同源重组(PEHR)是细菌基因组编辑的有效工具。我们之前开发并使用了假单胞菌特异性PEHR系统。然而,当使用PEHR系统进行假单胞菌基因组编辑时,假阳性可能是一个问题。在本研究中,我们将来自铜绿假单胞菌(PaeCas3c)的紧凑型Cascade-Cas3系统与假单胞菌特异性PEHR系统相结合,我们的重组分析结果表明,这种紧凑型Cascas3系统可以显著提高PEHR重组的准确性。
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引用次数: 4
Recent developments in the identification and biosynthesis of antitumor drugs derived from microorganisms 微生物来源的抗肿瘤药物的鉴定和生物合成的最新进展
Pub Date : 2022-12-01 DOI: 10.1016/j.engmic.2022.100047
Qi Gao , Sizhe Deng , Tianyu Jiang

Secondary metabolites in microorganisms represent a resource for drug discovery and development. In particular, microbial-derived antitumor agents are in clinical use worldwide. Herein, we provide an overview of the development of classical antitumor drugs derived from microorganisms. Currently used drugs and drug candidates are comprehensively described in terms of pharmacological activities, mechanisms of action, microbial sources, and biosynthesis. We further discuss recent studies that have demonstrated the utility of gene-editing technologies and synthetic biology tools for the identification of new gene clusters, expansion of natural products, and elucidation of biosynthetic pathways. This review summarizes recent progress in the discovery and development of microbial-derived anticancer compounds with emphasis on biosynthesis.

微生物中的次级代谢产物是药物发现和开发的资源。特别是,微生物衍生的抗肿瘤药物在世界范围内的临床应用。在此,我们对微生物衍生的经典抗肿瘤药物的发展进行了综述。目前使用的药物和候选药物从药理活性、作用机制、微生物来源和生物合成等方面进行了全面描述。我们进一步讨论了最近的研究,这些研究证明了基因编辑技术和合成生物学工具在鉴定新的基因簇、扩展天然产物和阐明生物合成途径方面的实用性。本文综述了近年来微生物衍生抗癌化合物的发现和开发进展,重点介绍了生物合成。
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引用次数: 2
Aquaculture sustainability through alternative dietary ingredients: Microalgal value-added products 通过替代膳食成分实现水产养殖的可持续性:微藻增值产品
Pub Date : 2022-12-01 DOI: 10.1016/j.engmic.2022.100049
John N. Idenyi , Jonathan C. Eya , Amechi S. Nwankwegu , Emeka G. Nwoba

Aquaculture contributes remarkably to the global economy and food security through seafood production, an important part of the global food supply chain. The success of this industry depends heavily on aquafeeds, and the nutritional composition of the feed is an important factor for the quality, productivity, and profitability of aquaculture species. The sustainability of the aquaculture industry depends on the accessibility of quality feed ingredients, such as fishmeal and fish oil. These traditional feedstuffs are under increasing significant pressure due to the rapid expansion of aquaculture for human consumption and the decline of natural fish harvest. In this review, we evaluated the development of microalgal molecules in aquaculture and expanded the use of these high-value compounds in the production of aquaculture diets. Microalgae-derived functional ingredients emerged as one of the promising alternatives for aquafeed production with positive health benefits. Several compounds found in microalgae, including carotenoids (lutein, astaxanthin, and β-carotene), essential amino acids (leucine, valine, and threonine), β-1–3-glucan, essential oils (docosahexaenoic acid and eicosapentaenoic acid), minerals, and vitamins, are of high nutritional value to aquaculture.

水产养殖通过海产品生产为全球经济和粮食安全做出了显著贡献,海产品生产是全球粮食供应链的重要组成部分。该行业的成功在很大程度上取决于水产饲料,而饲料的营养成分是影响水产养殖物种质量、生产力和盈利能力的重要因素。水产养殖业的可持续性取决于优质饲料成分的可及性,如鱼粉和鱼油。由于供人类食用的水产养殖的快速扩张和天然鱼类产量的下降,这些传统饲料面临着越来越大的压力。在这篇综述中,我们评估了微藻分子在水产养殖中的发展,并扩大了这些高价值化合物在水产养殖日粮生产中的应用。微藻衍生的功能性成分是水产饲料生产的一种有前景的替代品,对健康有积极的益处。微藻中发现的几种化合物,包括类胡萝卜素(叶黄素、虾青素和β-胡萝卜素)、必需氨基酸(亮氨酸、缬氨酸和苏氨酸)、β-1,3-葡聚糖、精油(二十二碳六烯酸和二十碳五烯酸)、矿物质和维生素,对水产养殖具有很高的营养价值。
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引用次数: 9
Bioproduction of monoterpene indole alkaloids in a single cell factory. 单细胞工厂中单萜吲哚生物碱的生物生产
Pub Date : 2022-10-01 eCollection Date: 2022-12-01 DOI: 10.1016/j.engmic.2022.100050
Jianping Huang, Shengxiong Huang

The de novo biosynthesis of vindoline and catharanthine, the direct precursors used for industrial production of the anti-cancer drug vinblastine, has been achieved in the yeast cell factory. To date, this is the longest natural product biosynthesis pathway that has been successfully transferred from plants to microorganisms, indicating the possibility of producing more than 3,000 other monoterpene indole alkaloids in yeast by synthetic genome engineering.

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引用次数: 0
Aquaculture sustainability through alternative dietary ingredients: Microalgal value-added products. 通过替代膳食成分实现水产养殖的可持续性:微藻增值产品
Pub Date : 2022-09-21 eCollection Date: 2022-12-01 DOI: 10.1016/j.engmic.2022.100049
John N Idenyi, Jonathan C Eya, Amechi S Nwankwegu, Emeka G Nwoba

Aquaculture contributes remarkably to the global economy and food security through seafood production, an important part of the global food supply chain. The success of this industry depends heavily on aquafeeds, and the nutritional composition of the feed is an important factor for the quality, productivity, and profitability of aquaculture species. The sustainability of the aquaculture industry depends on the accessibility of quality feed ingredients, such as fishmeal and fish oil. These traditional feedstuffs are under increasing significant pressure due to the rapid expansion of aquaculture for human consumption and the decline of natural fish harvest. In this review, we evaluated the development of microalgal molecules in aquaculture and expanded the use of these high-value compounds in the production of aquaculture diets. Microalgae-derived functional ingredients emerged as one of the promising alternatives for aquafeed production with positive health benefits. Several compounds found in microalgae, including carotenoids (lutein, astaxanthin, and β-carotene), essential amino acids (leucine, valine, and threonine), β-1-3-glucan, essential oils (docosahexaenoic acid and eicosapentaenoic acid), minerals, and vitamins, are of high nutritional value to aquaculture.

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引用次数: 0
Methods of DNA introduction for the engineering of commensal microbes. 共生微生物工程中DNA导入方法的研究
Pub Date : 2022-09-12 eCollection Date: 2022-12-01 DOI: 10.1016/j.engmic.2022.100048
Dake Liu, Nicole E Siguenza, Amir Zarrinpar, Yousong Ding

The microbiome is an essential component of ecological systems and is comprised of a diverse array of microbes. Over the past decades, the accumulated observational evidence reveals a close correlation between the microbiome and human health and disease. Many groups are now manipulating individual microbial strains, species and the community as a whole to gain a mechanistic understanding of the functions of the microbiome. Here, we discuss three major approaches for introducing DNA to engineer model bacteria and isolated undomesticated bacteria, including transformation, transduction, and conjugation. We provide an overview of these approaches and describe the advantages and limitations of each method. In addition, we highlight examples of human microbiome engineering using these approaches. Finally, we provide perspectives for the future of microbiome engineering.

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引用次数: 0
Recent developments in the identification and biosynthesis of antitumor drugs derived from microorganisms. 微生物源抗肿瘤药物的鉴定与生物合成研究进展
Pub Date : 2022-09-03 eCollection Date: 2022-12-01 DOI: 10.1016/j.engmic.2022.100047
Qi Gao, Sizhe Deng, Tianyu Jiang

Secondary metabolites in microorganisms represent a resource for drug discovery and development. In particular, microbial-derived antitumor agents are in clinical use worldwide. Herein, we provide an overview of the development of classical antitumor drugs derived from microorganisms. Currently used drugs and drug candidates are comprehensively described in terms of pharmacological activities, mechanisms of action, microbial sources, and biosynthesis. We further discuss recent studies that have demonstrated the utility of gene-editing technologies and synthetic biology tools for the identification of new gene clusters, expansion of natural products, and elucidation of biosynthetic pathways. This review summarizes recent progress in the discovery and development of microbial-derived anticancer compounds with emphasis on biosynthesis.

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引用次数: 0
期刊
Engineering Microbiology
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