Methylation of flavonoids: Chemical structures, bioactivities, progress and perspectives for biotechnological production.

Among the natural products, flavonoids have been particularly attractive, highly studied and become one of the most important promising agent to treat cancer, oxidant stress, pathogenic bacteria, inflammations, cardio-vascular dysfunctions, etc. Despite many promising roles of flavonoids, expectations have not been fulfilled when studies were extended to the in vivo condition, particularly in humans. Instability and very low oral bioavailability of dietary flavonoids are the reasons behind this. Researches have demonstrated that the methylation of these flavonoids could increase their promise as pharmaceutical agents leading to novel applications. Methylation of the flavonoids via theirs free hydroxyl groups or C atom dramatically increases their metabolic stability and enhances the membrane transport, leading to facilitated absorption and highly increased oral bioavailability. In this paper, we concentrated on analysis of flavonoid methoxides including O- and C-methoxide derivatives in aspect of structure, bioactivities and description of almost all up-to-date O- and C-methyltransferases' enzymatic characteristics. Furthermore, modern biological approaches for synthesis and production of flavonoid methoxides using metabolic engineering and synthetic biology have been focused and updated up to 2015. This review will give a handful information regarding the methylation of flavonoids, methyltransferases and biotechnological synthesis of the same.