Flavonoid Production: Current Trends in Plant Metabolic Engineering and De Novo Microbial Production

Abstract

Flavonoids are secondary metabolites that represent a heterogeneous family of plant polyphenolic compounds. Recent research has determined that the health benefits of fruits and vegetables, as well as the therapeutic potential of medicinal plants, are based on the presence of various bioactive natural products, including a high proportion of flavonoids. With current trends in plant metabolite research, flavonoids have become the center of attention due to their significant bioactivity associated with anti-cancer, antioxidant, anti-inflammatory, and anti-microbial activities. However, the use of traditional approaches, widely associated with the production of flavonoids, including plant extraction and chemical synthesis, has not been able to establish a scalable route for large-scale production on an industrial level. The renovation of biosynthetic pathways in plants and industrially significant microbes using advanced genetic engineering tools offers substantial promise for the exploration and scalable production of flavonoids. Recently, the co-culture engineering approach has emerged to prevail over the constraints and limitations of the conventional monoculture approach by harnessing the power of two or more strains of engineered microbes to reconstruct the target biosynthetic pathway. In this review, current perspectives on the biosynthesis and metabolic engineering of flavonoids in plants have been summarized. Special emphasis is placed on the most recent developments in the microbial production of major classes of flavonoids. Finally, we describe the recent achievements in genetic engineering for the combinatorial biosynthesis of flavonoids by reconstructing synthesis pathways in microorganisms via a co-culture strategy to obtain high amounts of specific bioactive compounds

Bioactive Compounds from Kalanchoe Genus Potentially Useful for the Development of New Drugs

“…In fact, understanding the enzymes involved in the biosynthesis pathway of bioactive compounds as well as the genes implicated in their biosynthesis opens new opportunities to obtain bioactive molecules at a large scale. Several recent studies have described how biotechnological approaches can be applied to increase the content of secondary metabolites in plants (in situ) or how plant cells, tissues, and organelles, as well as microorganisms (e.g., Escherichia coli ), can be used as platforms to produce these compounds in vitro [ 142 ]. Indeed, in vitro cultures of Kalanchoe plants are well established.…”

High-Level De Novo Production of (2S)-Eriodictyol in Yarrowia Lipolytica by Metabolic Pathway and NADPH Regeneration Engineering

“…6 Therefore, high-level production of (2S)-eriodictyol would significantly facilitate the advancements of pharmaceutical and food applications. 7 Plant extraction and chemical synthesis are the primary methods for obtaining (2S)-eriodictyol, but these approaches suffer from issues such as expensive raw materials, low titer, and environmental pollution. 8 In contrast, the microbial synthesis of (2S)-eriodictyol has the obvious advantages of high efficiency, low pollution, and low production cost, making it a sustainable alternative method.…”

“…Consuming foods rich in (2 S )-eriodictyol has been confirmed to be beneficial for physical health . Therefore, high-level production of (2 S )-eriodictyol would significantly facilitate the advancements of pharmaceutical and food applications . Plant extraction and chemical synthesis are the primary methods for obtaining (2 S )-eriodictyol, but these approaches suffer from issues such as expensive raw materials, low titer, and environmental pollution .…”

Enhancing Glycosylation of Flavonoids by Engineering the Uridine Diphosphate Glucose Supply in Escherichia coli

“…Flavonoid glycosides can be divided into flavonoid O - and C -glycosides according to the flavonoid and the glycosyl group connected via C–O and C–C bonds . Vitexin (apigenin-8- C -glucoside), orientin (luteolin-8- C -glucoside), afzelin (kaempferol-3- O -rhamnoside), quercitrin (quercetin-3- O -rhamnoside), trifolin (kaempferol-3- O -galactoside), and hyperoside (quercetin-3- O -galactoside) are natural flavonoid glycosides in plants and active ingredients in many Chinese herbs. − These flavonoid glycosides are receiving increasing attention as a result of their broad pharmacological effects, including antioxidant, neuroprotective, anticancer, antihyperalgesic, and anti-inflammatory activities. − …”