**1. Introduction**

262 Biochemistry

Wolterink-van Loo, S., Levisson, M., Cabrières, M.C., Franssen, M.C.R., & van der Oost, J.

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(2008). Characterization of a thermostable dihydrodipicolinate synthase from *Thermoanaerobacter tengcongensis. Extremophiles*, Vol.12, No.3, (May 2008), pp. 461-

> Flavonoids comprise a group of plant polyphenols with a broad spectrum of biological activities. They have been shown to exert beneficial effects on human health and play an important role in prevention and/or treatment of several serious diseases, such as cancer, inflammation and cardiovascular disease (Middleton et al., 2000; Rice-Evans, 2001). Flavonoids are important beneficial components of food, pharmaceuticals, cosmetics and various commodity preparations due to their antimutagenic, hepatoprotective (Stefani et al., 1999), antiallergic (Berg & Daniel, 1988), antiviral (Middleton & Chithan, 1993) and antibacterial activity (Tarle & Dvorzak, 1990; Tereschuk et al., 1997; Singh & Nath, 1999; Quarenghi et al., 2000; Rauha et al., 2000). They are known to inhibit nucleic acid synthesis (Plaper et al., 2003; Cushnie & Lamb, 2006), cause disturbance in membranes (Stepanovic et al., 2003; Stapleton et al., 2004; Cushnie & Lamb, 2005) and affect energy metabolism (Haraguchi et al., 1998). But the most studied activity is their antioxidant action since they can readily eliminate reactive oxygen and nitrogen species or degradation products of lipid peroxidation and are thus effective inhibitors of oxidation (Ross & Kasum, 2002).

> However, their commercial applications are limited due to low solubility in lipophilic environment and low availability for a living organism. Although aglycons, prenylated and methoxylated flavonoid derivatives may be implemented into such systems, they are rarely found in nature and are often unstable. In some plant species, the last step in the flavonoid biosynthesis is terminated by acylation which is known to increase solubility and stability of glycosylated flavonoids in lipophilic systems. Selectively acylated flavonoids with different aliphatic or aromatic acids may not only improve physicochemical properties of these molecules (Ishihara & Nakajima, 2003) but also introduce various beneficial properqties to the maternal compound. These include penetration through the cell membrane (Suda et al., 2002; Kodelia et al., 1994) enhanced antioxidant activity (Viskupicova et al., 2010; Katsoura et al., 2006; Mellou et al., 2005), antimicrobial (Mellou et al., 2005), anti-proliferative (Mellou et al., 2006) and cytogenic (Kodelia et al., 1994) effect and improvement of thermostability and light-resistivity of certain flavonoids.

In nature, flavonoid acylation is catalyzed by various acyltransferases which are responsible for the transfer of aromatic or aliphatic acyl groups from a CoA-donor molecule to hydroxyl residues of flavonoid sugar moieties (Davies & Schwinn, 2006). Acylation is widespread especially among anthocyanins; more than 65% are reported to be acylated (Andersen & Jordheim, 2006). While the exact role of plant acylation is not yet fully understood, it is known that these modifications modulate the physiological activity of the resulting flavonoid ester by altering solubility, stability, reactivity and interaction with cellular targets (Ferrer et al., 2008). Acylation might be a prerequisite molecular tag for efficient vacuolar uptake of flavonoids (Kitamura, 2006; Nakayama et al., 2003). Some acylated flavonoids have been found to be involved in plant-insect interactions; they act as phytoalexins, oviposition stimulants, pollinator attractants (Iwashina, 2003), and insect antifeedants (Harborne & Williams, 1998). With respect to novel biological activities, acylation of flavonoids can result in changes in pigmentation (Bloor, 2001), insect antifeedant activity (Harborne & Williams, 1998) and antioxidant properties (Alluis & Dangles, 1999).

Over the past 15 years, there has been a substantial effort to take advantage of this naturally occurring phenomenon and to implement acylation methods into laboratories. However, the use of acyltransferases as modifying agents is rather inconvenient, as they require corresponding acylcoenzyme A, which must be either in stoichiometric amounts or regenerated *in situ*. Natural acyltransferases and cell extracts from *Ipomoea batatas* and *Perilla frutescens* containing acyltransferases were applied for selective flavonoid modification with aromatic acids (Tab.1) (Nakajima et al., 2000; Fujiwara et al., 1998).


Table 1. Acyltransferase catalysis of flavonoid acylation and their nature sources.

To solve this problem, the chemical approach was first investigated. It possessed a low degree of regioselectivity of esterification and drastic reaction conditions had to be applied (Patti et al., 2000). Later on, hydrolytic enzymes (lipases, esterases and proteases) have been recognized as useful agents due to their large availability, low cost, chemo-, regio- and enantioselectivity, mild condition processing and no need of cofactors (Collins & Kennedy, 1999; Nagasawa & Yamada, 1995).

Since the enzymatic preparation of flavonoid derivatives is a matter of several years, commercial applications have just been emerging. There are several patented inventions available to date, oriented on the flavonoid ester production and their use for the manufacture of pharmaceutical, dermopharmaceutical, cosmetic, nutritional or agri-foodstuff compositions (Fukami et al., 2007; Moussou et al., 2004, 2007; Ghoul et al., 2006; Bok et al., 2001; Perrier et al., 2001; Otto et al., 2001; Nicolosi et al., 1999; Sakai et al., 1994).

This review presents available information on enzyme-mediated flavonoid acylation *in vitro*, emphasizing reaction parameters which influence performance and regioselectivity of the enzymatic reaction. In the second part, the paper focuses on biological effects of synthesized flavonoid esters as well as of those isolated from nature. Finally, the paper ends with application prospects of acylated flavonoids in the food, pharmaceutical and cosmetic industry.
