**1. Introduction**

Climate change is the most serious threat to current human culture. Escalating global food demand and ever-increasing global warming put humanity in jeopardy. According to ongoing global temperature analysis carried out by NASA's Goddard Institute for Space Studies (GISS) scientists, the average global temperature has increased by about 1 ◦C since 1880 [1], and it is estimated that every 2 ◦C rise in global temperature will cause on hundred million human deaths and bring millions of species to the brink of extinction [2]. After fossil fuel burning for energy generation, agriculture is the second-largest contributor to climate change through the emission of greenhouse gases (GHGs) including carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) [3]. Commercial fertilizers are very convenient, easy to handle and a rapid source of soil nutrient recharge, however, the toxic and residual effects of synthetic chemicals have altered thinking around this. It is estimated that reductions in mineral fertilizer use could lead to a 20% reduction in GHG emissions [4]. As the world warms, there is an immediate need to adjust what have become inadequate and inappropriate policies. There is an urgency to develop ecofriendly land practices and more sustainable agriculture. The implementation of biobased products, for example, ushering in the use of organic farming,

biofertilizers and biocontrol techniques, will be a progressive step towards sustainable global food security. In this review, we focused on a specific type of biostimulant, flavonoids, and their role in sustainable agriculture. Flavonoids are examples of a versatile set of low molecular weight secondary metabolites with a polyphenolic structure, involved in plant physiological functions, often demonstrating protective effects against biotic and abiotic stresses including UV-B radiation [5], salt stress [6] and drought [7], at least in part by detoxifying the Reactive Oxygen Species (ROS) produced under stress conditions in plants [8,9]. Flavonoids also play a crucial role in plant–microbe associations, predominantly plant–rhizobia and arbuscular mycorrhizal symbioses [10]. Certain flavonoids act as signaling compounds triggering nodule induction by inducing transcription of *nod* genes in rhizobia, the first step in legume–rhizobia symbiotic relationships [11]. In addition, some flavonoids act to combat certain pests and pathogens [12]. Some classes of flavonoids act as color pigments, producing specific hues in leaves and flower petals, helping plants attract pollinators [13]. Moreover, flavonoids have indirect effects on nutrient supply and availability by enhancing mycorrhizal symbioses and colonization of the rhizosphere by beneficial microorganisms [14].

#### **2. Biosynthesis and Classification of Flavonoids**

The biosynthesis of distinct flavonoid-based compounds is the result of condensation of one molecule of 4-coumaroyl-CoA (6-carbon) and three molecules of malonyl-CoA, carried out by the enzyme chalcone synthase (CHS). The two major precursors originate from two different pathways of cellular metabolism: the acetate pathway and shikimate pathway providing ring A and ring B, respectively, with chain linkages forming ring C. Ring A is generated from malonyl-CoA synthesized by carboxylation of acetyl-CoA via the acetate pathway, however, ring B along with the linking chain (ring C) is synthesized from coumaroyl-CoA via the shikimate pathway (Figure 1). Coumaroyl-CoA is generated directly from the amino acid phenylalanine by three enzymatic reactions of the phenylpropanoid pathway [15].

The condensation of these aromatic rings by these pathways results in the synthesis of chalcone which will then form flavanone after isomerase-catalyzed cyclization. The later compounds undergo further modifications such as hydroxylation, glycosylation or methylation resulting in the enormous range of flavonoid colors we see today.

Flavonoids are the largest family of natural products; more than nine thousands of these phenolic substances have been found in various plants [16]. Flavonoids have a basic structure containing three phenolic rings, namely A (6 carbon) and B (6-carbon) linked with the central C (3-carbon) ring; C6-C3-C6 which can produce several derivatives and sub-class compounds with distinct substitutions in the basic structure [17]. The major subgroups of flavonoids are; flavonols, flavones, flavanones, flavanonols, flavanols, anthocyanins, isoflavonoids and chalcones [18]. However, based on the attachment of the B ring to the C ring, flavonoids have been classified into three major subgroups: Flavonoids (2-phenylbenzopyrans): The B ring is attached on 2-position of ring C), Isoflavonoids (3-benzopyrans): The B ring is attached on 3-position of ring C) and Neoflavonoids (4-benzopyrans: unlike isoflavonoids; the B ring is attached at 4-position of C ring) [19].

**Figure 1.** Biosynthesis of flavonoids.

#### *2.1. Flavonols*

Flavonols are the most abundant flavonoids in plants. The most studied subclasses of flavonols are the quercetins, kaempferols, myricetins and fisetins; distinctions in the structures of each subclass are shown in Figure 2. The substitution patterns in quercetins and kaempferols are 3,5,7,3 ,4 -OH and 3,5,7,4 -OH, respectively. These are very often found in plants as glycosides. The major dietary sources of flavonols are fruits and vegetables, predominantly onions, but also including the apple, strawberry, lettuce and other leafy vegetables. In addition, black and green tea and red wine are also rich sources of flavonols. In general, soft fruits, leaves of medicinal plants and green leafy vegetables have greater levels of flavonoids than other vegetable and fruit plants [20]. However, cooking may lower the concentration of flavonols in vegetables such as tomato and onion [21].

**Figure 2.** Flavonols: chemical structures, types and substitution positions in the basic skeleton.
