33 rpm acetate master8/31/2023 ![]() ![]() ![]() Therefore, utilizing acetate for microbial naringenin production would be an effective strategy for the construction of economically viable bioprocesses and reducing the cost of substrates. Furthermore, acetate is an eco-friendly renewable resource that can be produced from fermentation of industrial by-products and syngas. In this regard, acetate has emerged as a promising carbon source, showing high potential for industrial use, since it can plentifully be obtained from inexpensive natural sources, such as lignocellulose biomass and carbon dioxide, at reasonable costs. For microbial production of naringenin, low-cost and abundant feedstock would be required to achieve economically feasible and sustainable bioprocesses. Accordingly, attempts have been made to produce naringenin by microbial biosynthesis via heterologous production in Escherichia coli and Saccharomyces cerevisiae with advances in metabolic engineering and synthetic biology. Traditionally, naringenin is extracted from plants however, the conventional method has been limited by low yield from natural sources, complicated purification involved in a large number of solvents, and scalability issues. In addition, it has value as a key scaffold molecule for the biosynthesis of various flavonoids. Naringenin, a secondary metabolite that can be obtained from natural plants, is a value-added chemical with high pharmaceutical applicability, such as oxygen radical elimination, and anti-inflammatory and antiviral properties. This study was the first attempt of naringenin production from acetate and suggested the potential of biosynthesis of various flavonoids derived from naringenin using acetate. ConclusionsĬollectively, we demonstrated efficient flux rerouting for maximum naringenin production from acetate in E. Consequently, the flux-optimized strain exhibited a significant increase in naringenin production, a 27.2-fold increase (with a 38.3-fold increase of naringenin yield on acetate) over that by the unoptimized strain, producing 97.02 mg/L naringenin with 21.02 mg naringenin/g acetate, which is a competitive result against those in previous studies on conventional substrates, such as glucose. ![]() Precise rerouting at the OAA node for enhanced acetyl-CoA was conducted, avoiding extensive loss of OAA by fine-tuning the expression of pckA (encoding phosphoenolpyruvate carboxykinase) with flux redistribution between naringenin biosynthesis and cell growth at the isocitrate node. This study identified the isocitrate and oxaloacetate (OAA) nodes as key regulatory nodes for the naringenin production using acetate. Accordingly, appropriate rerouting of TCA cycle intermediates from anaplerosis into naringenin biosynthesis via acetyl-CoA replenishment would be required. While acetyl-CoA is a key precursor for naringenin production, carbon flux between the TCA cycle and anaplerosis is effectively regulated at the isocitrate node through glyoxylate shunt in acetate metabolism. For the efficient production of naringenin using acetate, identification of the appropriate regulatory node of carbon flux in the biosynthesis of naringenin from acetate would be important. From this perspective, utilizing acetate for naringenin production could be an effective strategy, with the advantages of both low-cost and abundant feedstock. In the microbial fermentation, a cheap and abundant feedstock is required to achieve an economically feasible bioprocess. Microbial production of naringenin has received much attention owing to its pharmaceutical applicability and potential as a key molecular scaffold for various flavonoids. ![]()
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