**3. The production of flavonoids by microorganisms**

Since plants and chemical synthesis produce low levels of flavonoids, researchers have turned to open fermentation and metabolic engineering to produce flavonoids in microorganisms [38]. Toxic chemicals and extreme reaction conditions are necessary for the chemical synthesis of flavonoids [39]. Combinatorial biosynthesis offers an advantage in the production of rare and expensive natural products, thanks to the rapid development of molecular biology tools and genome information flooding from a wide variety of organisms. Unlike the tedious blocking and de-blocking steps common to organic synthesis, it also allows for simple and complex transformations [40]. In addition to *Escherichia coli*, *Phellinus igniarius, Saccharomyces cerevisiae* and *Streptomyces venezuelae*, and, a medicinal mushroom, flavonoids can also be produced by additional prokaryotes and eukaryotes [41], a variety of other cultures have been used to produce flavonoids.
