Journal of Energy Bioscience 2024, Vol.15, No.6, 378-387 http://bioscipublisher.com/index.php/jeb 378 Research Insight Open Access Unravelling the Biosynthesis of Isoflavones in Soybeans From a Metabolic Perspective Dandan Huang Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China Corresponding email: dandan.huang@hibio.org Journal of Energy Bioscience, 2024, Vol.15, No.6 doi: 10.5376/jeb.2024.15.0032 Received: 13 Oct., 2024 Accepted: 18 Nov., 2024 Published: 22 Dec., 2024 Copyright © 2024 Huang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Huang D.D., 2024, Unravelling the biosynthesis of isoflavones in soybeans from a metabolic perspective, Journal of Energy Bioscience, 15(6): 378-387 (doi: 10.5376/jeb.2024.15.0032) Abstract Isoflavones are mainly found in soybeans and are an important secondary metabolite. They not only play an important role in the plant defense system, but also reduce health risks such as hormone-dependent cancer, osteoporosis, and cardiovascular disease. The synthesis of isoflavones starts from phenylpropanoid metabolism, in which the core enzymes chalcone synthase (CHS) and isoflavone synthase (IFS) combine to form a metabolic complex to promote efficient metabolic flow. The transcriptional regulation of this pathway involves multiple key transcription factors (such as GmMYB29 and GmZFP7). Environmental factors such as temperature, light, soil, and water can affect the biosynthesis and accumulation of isoflavones, among which the plant hormone signaling pathway plays an important regulatory role. In recent years, with the advancement of genetic engineering technology, as well as the improvement of CRISPR/Cas9 gene editing and synthetic biology strategies, we have the hope of achieving precise regulation of isoflavone biosynthesis genes. But at the same time, research in this field still faces many challenges. The impact of environmental conditions on metabolite accumulation, the complexity of biosynthetic pathways, and the metabolic trade-offs that may be caused by metabolic flow redistribution will all have an impact on the research. In the future, we hope to integrate multiple omics technologies, systematically analyze the regulatory network of isoflavone biosynthesis, optimize metabolic engineering strategies, improve the controllable accumulation of isoflavones, and reduce the uncertainty caused by environmental factors. Through these efforts, we will improve the environmental adaptability of soybeans and further expand the potential application of isoflavones in functional foods and human health. Keywords Isoflavone biosynthesis; Phenylpropanoid pathway; Metabolic engineering; Soybean secondary metabolites; Transcriptional regulation 1 Introduction Isoflavones are mainly found in leguminous plants (mainly in soybeans) and are secondary metabolites. They play an important role in plant defense mechanisms, can enhance plant disease resistance and stress resistance, and are very important for soybean production and development (Veremeichik et al., 2020; Sohn et al., 2021). In addition to their role in plants, isoflavones are also important in the field of human health due to their estrogenic activity and antioxidant properties. Studies have shown that the intake of isoflavones is closely related to a reduced risk of hormone-dependent cancers, osteoporosis, menopausal syndrome, and cardiovascular disease. Therefore, isoflavones are also important bioactive components in the human diet (Jung et al., 2000; Sohn et al., 2021). The biosynthesis of soy isoflavones is a complex process branching from the phenylpropanoid metabolic pathway, involving multiple key enzymes. Among them, Isoflavone Synthase (IFS) catalyzes the initial step of the biosynthesis pathway, while Chalcone Synthase (CHS), Chalcone Reductase (CHR), Chalcone Isomerase (CHI) and other enzymes jointly participate in the regulation of this pathway and form metabolic complexes anchored to the endoplasmic reticulum (Jung et al., 2000; Dastmalchi et al., 2016). In addition, the transcriptional regulation of this pathway is finely regulated by multiple transcription factors, including GmMYB29 of the R2R3-MYB family and GmZFP7 of the C2H2 zinc finger transcription factor, which affect the biosynthesis of isoflavones by regulating the expression levels of key enzyme genes (Chu et al., 2017; Feng et al., 2022). At present, metabolic engineering has become an important strategy for increasing the content of soy isoflavones. Relevant studies have
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