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pathway. We further assemble an exhaustive map of flavonoid biosynthesis in plants comprising eight branches (stilbene, aurone, flavone, isoflavone, flavonol, phlobaphene, proanthocyanidin, and anthocyanin biosynthesis) and 4 critical intermediate metabolites (chalcone, flavanone, dihydroflavonol, and PPARδ Purity & Documentation leucoanthocyanidin). This evaluation affords a complete overview with the existing expertise concerning flavonoid biosynthesis, and gives the theoretical basis for additional elucidating the pathways involved within the biosynthesis of flavonoids, that will aid in better understanding their functions and potential makes use of.Citation: Liu, W.; Feng, Y.; Yu, S.; Fan, Z.; Li, X.; Li, J.; Yin, H. The Flavonoid Biosynthesis Network in Plants. Int. J. Mol. Sci. 2021, 22, 12824. doi.org/10.3390/ ijms222312824 Academic Editor: Guido R. M. M. Haenen Received: 21 October 2021 Accepted: 18 November 2021 Published: 26 NovemberKeywords: flavonoids; biosynthesis; molecular structure; biosynthetic enzyme; gene regulation1. Introduction Flavonoids comprise a group of phenylpropanoids that, as water-soluble pigments, are stored in the vacuoles of plant cells [1]. Except for stilbenes (a class of flavonoids), which has a C6-C2-C6 structure (Figure 1), the basic structure of flavonoids consists of a C6-C3-C6 carbon skeleton (Figure 1) comprising two 6-carbon benzene rings (rings A and B) linked by a 3-carbon heterocyclic ring (ring C) [2]. Flavonoids could be classified into 12 subgroups–chalcones, stilbenes, aurones, flavanones, flavones, isoflavones, phlobaphenes, dihydroflavonols, flavonols, leucoanthocyanidins, proanthocyanidins, and anthocyanins (Figure 1) [3,4]–based around the degree of oxidation in the heterocyclic ring plus the number of hydroxyl or methyl groups on the benzene ring. In the exact same time, different modifications (glycosylation, acylation, and other folks) and molecular polymerization result in the formation of a sizable variety of flavonoid compounds [5,6]. To date, greater than 9000 plant flavonoids have been isolated and identified [7]. Some flavonoids play a crucial role in plant development and defense. Flavonoids constitute certainly one of the key pigments in plants, which include anthocyanins (red, orange, blue, and purple pigments); chalcones and aurones (yellow pigments); and flavonols and flavones (white and pale-yellow pigments), which impart on plants a wide number of colors [8]. Flavonoids, as phytoalexins or antioxidants, have reactive oxygen species (ROS) scavenging potential [9] and safeguard plants against harm from biotic and abiotic stresses, such as UV irradiation, cold strain, pathogen infection, and insect feeding [102]. In plants, flavonoids can also act as signaling PI3Kγ medchemexpress molecules, attracting insects for pollination and participating in auxin metabolism [13]. Plant flavonoids also have widespread use in everyday life, suchPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Copyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is definitely an open access write-up distributed beneath the terms and circumstances with the Inventive Commons Attribution (CC BY) license ( creativecommons.org/licenses/by/ four.0/).Int. J. Mol. Sci. 2021, 22, 12824. doi.org/10.3390/ijmsmdpi/journal/ijmsInt. J. Mol. Sci. 2021, 22, x FOR PEER Review Int. J. Mol. Sci. 2021, 22,2 of 18 two ofparticipating in auxin metabolism [13]. Plant flavonoids also have widespread use in day-to-day as for meals and medicinal purposes.

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