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Microbial production of sialic acid and sialylated human milk oligosaccharides: Advances and perspectives.
Zhang, X, Liu, Y, Liu, L, Li, J, Du, G, Chen, J
Biotechnology advances. 2019;(5):787-800
Abstract
Sialic acids (SAs) are important functional sugars, and monomers of sialylated human milk oligosaccharides (sialylated HMOs or sialyllactoses), which are crucial for improving infant development and can facilitate infant brain development, maintain brain health, and enhance immunity. The most common form of SA is N-acetylneuraminic acid (NeuAc), and the main forms of sialyllactoses are 6'-sialyllactose (6'-SL) and 3'-sialyllactose (3'-SL). As functional food additive, the demand for NeuAc and sialyllactoses will continuously increase due to their wide and important fields of application. However, NeuAc and sialyllactoses produced by traditional extraction methods are inefficient and may cause allergen contamination, and cannot keep up with the rapidly increasing market demand. Therefore, the production of NeuAc and sialyllactoses by sustainable biotechnological methods have attracted increasing attention. In particular, the development of metabolic engineering and synthetic biology techniques and strategies have promoted efficient biosynthesis of NeuAc and sialyllactoses. In this review, we first discussed the application of NeuAc and sialyllactoses. Secondly, metabolic engineering and protein engineering-fueled progress of whole-cell catalysis and de novo synthesis of NeuAc and sialyllactoses were systematically summarized and compared. Furthermore, challenges of efficient microbial production of NeuAc and sialyllactoses as well as strategies for overcoming the challenges were discussed, such as clustered regularly interspaced short palindromic repeats interference (CRISPRi)-aided identification of key precursor transport pathways, synergistically debottleneck of kinetic and thermodynamic limits in synthetic pathways, and dynamic regulation of metabolic pathways for balancing cell growth and production. We hope this review can further facilitate the understanding of limiting factors that hampered efficient production of sialic acid and sialyllactoses, as well as contribute to the development of strategies for the construction of efficient production hosts for high-level production of sialic acid and sialyllactose based on synthetic biology tools and strategies.
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2.
Recent advances in production of 5-aminolevulinic acid using biological strategies.
Kang, Z, Ding, W, Gong, X, Liu, Q, Du, G, Chen, J
World journal of microbiology & biotechnology. 2017;(11):200
Abstract
5-Aminolevulinic acid (5-ALA) is the precursor for the biosynthesis of tetrapyrrole compounds and has broad applications in the medical and agricultural fields. Because of the disadvantages of chemical synthesis methods, microbial production of 5-ALA has drawn intensive attention and has been regarded as an alternative in the last years, especially with the rapid development of metabolic engineering and synthetic biology. In this mini-review, recent advances on the application and microbial production of 5-ALA using novel biological approaches (such as whole-cell enzymatic-transformation, metabolic pathway engineering and cell-free process) are described and discussed in detail. In addition, the challenges and prospects of synthetic biology are discussed.
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3.
Biotechnological production of alpha-keto acids: Current status and perspectives.
Song, Y, Li, J, Shin, HD, Liu, L, Du, G, Chen, J
Bioresource technology. 2016;:716-724
Abstract
Alpha-keto (α-keto) acids are used widely in feeds, food additives, pharmaceuticals, and in chemical synthesis processes. Although most α-keto acids are currently produced by chemical synthesis, their biotechnological production from renewable carbohydrates is a promising new approach. In this mini-review, we first present the different types of α-keto acids as well as their applications; next, we summarize the recent progresses in the biotechnological production of some important α-keto acids; namely, pyruvate, α-ketoglutarate, α-ketoisovalerate, α-ketoisocaproate, phenylpyruvate, α-keto-γ-methylthiobutyrate, and 2,5-diketo-d-gluconate. Finally, we discuss the future prospects as well as favorable directions for the biotechnological production of keto acids that ultimately would be more environment-friendly and simpler compared with the production by chemical synthesis.
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4.
Small RNA regulators in bacteria: powerful tools for metabolic engineering and synthetic biology.
Kang, Z, Zhang, C, Zhang, J, Jin, P, Zhang, J, Du, G, Chen, J
Applied microbiology and biotechnology. 2014;(8):3413-24
Abstract
Small RNAs, a large class of ancient posttranscriptional regulators, have recently attracted considerable attention. A plethora of small RNAs has been identified and characterized, many of which belong to the major small noncoding RNA (sRNA) or riboswitch families. It has become increasingly clear that most small RNAs play critical regulatory roles in many processes and are, therefore, considered to be powerful tools for metabolic engineering and synthetic biology. In this review, we describe recent achievements in the identification, characterization, and application of small RNAs. We give particular attention to advances in the design and synthesis of novel sRNAs and riboswitches for metabolic engineering. In addition, a novel strategy for hierarchical control of global metabolic pathways is proposed.
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5.
Structure, mechanism and regulation of an artificial microbial ecosystem for vitamin C production.
Zou, W, Liu, L, Chen, J
Critical reviews in microbiology. 2013;(3):247-55
Abstract
At present, the modern two-step fermentation process is one of the major approaches for the industrial production of vitamin C. The key step in this process is the conversion of L-sorbose to 2-keto-L-gulonic acid (2-KLG), the vitamin C precursor, which is accomplished by an artificial microbial ecosystem consisting of Ketogulonicigenium vulgare and Bacillus megaterium. This review describes current progress in understanding this ecosystem, not only the individual physiological characteristics of the two strains, but also the interactions between them. Special emphasis is placed on recent systems biology studies of the ecosystem. We also discuss the regulation and improvement of this ecosystem, including analysis of the fermentation medium components and genetic engineering and optimum fermentative strategies. Finally, perspectives on the knowledge and engineering of this important artificial microbial ecosystem are discussed.
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6.
Metabolic engineering of microorganisms for vitamin C production.
Zhou, J, Du, G, Chen, J
Sub-cellular biochemistry. 2012;:241-59
Abstract
Vitamin C, an important organic acid, is widely used in the industries of pharmaceuticals, cosmetics, food, beverage and feed additives. Compared with the Reichstein method, biotechnological production of vitamin C is an attractive approach due to the low cost and high product quality. In this chapter, biosynthesis of vitamin C, including one-step fermentation processes and two-step fermentation processes are discussed and compared. Furthermore, the prospects of the biotechnological production of vitamin C are also presented.