Microbial production of 4-hydroxybenzylidene acetone, the direct precursor of raspberry ketone

Abstract

Aims: To investigate the enzymatic aldol reaction between acetone as a donor and 4‐hydroxybenzaldehyde as a receptor to generate 4‐(4‐hydroxyphenyl)‐but‐3‐ene‐2‐one or 4‐hydroxybenzylidene acetone, the direct precursor of 4‐(4‐hydroxyphenyl)‐butan‐2‐one or raspberry ketone, using different species of filamentous fungi and bacteria. Methods and Results: Different classes of micro‐organisms were tested in a medium containing mainly acetone and 4‐hydoxybenzaldehyde. Of the micro‐organisms tested, only bacteria were able to synthesize significant amounts of 4‐hydroxybenzylidene acetone, ranging from 15 to 160 mg l−1 after 21 h of bioconversion, as a function of the bacteria tested. Conclusions: The biological production of 4‐hydroxybenzylidene acetone has been described with bacteria possessing 2‐deoxyribose‐5‐phosphate aldolase (DERA, EC 4·1·2·4). This result suggests that DERA is involved in the catalytic aldolization of precursors for the production of 4‐hydroxybenzylidene acetone. Significance and Impact of the Study: Raspberry ketone or frambinone represents a total market value of between €6 million and €10 million. The possibility of producing its direct precursor through a simple process using bacteria is of considerable interest to the flavour market and the food industry as a whole. This paper broadens the spectrum for the use of aldolase to achieve the biological synthesis of compounds of interest.

Trading off stability against activity in extremophilic aldolases

“…The enzyme catalyzes the formation of C-C bonds between an aldehyde as an electrophile and acetaldehyde as a nucleophile in a highly stereoselective manner 12 . Thus, it has become an important alternative to chemical methods to synthesize chiral building blocks for natural products 13 14 . During the past decade, four crystal structures of hyperthermophilic DERAs were solved 15 16 17 , but thus far no structure of psychrophilic origin is available.…”

Production of 3-hydroxy-γ-decalactone, the precursor of two decenolides with flavouring properties, by the yeast Yarrowia lipolytica

“…The whole world of flavours and fragrances is currently seeking new compounds that could be used in aroma formulations (see for instance recent works on the production of raspberry ketone, 6-pentyl-alphapyrone, ionones, dihydroactinidiolide, damascenone, etc. [5][6][7][8][9][10][11]). The two decenolides can already accumulate, although in very low amounts, with the yeast Yarrowia lipolytica [3,4].…”

Bioconversion to Raspberry Ketone is Achieved by Several Non-related Plant Cell Cultures

“…The characteristic aroma component in raspberry ( Rubus idaeus ) fruits is 4-(4-hydroxyphenyl)butan-2-one, also called raspberry ketone or frambinone ( Feron et al, 2007 ). The amount of raspberry ketone in raspberry fruits is only around 1–4 mg/kg fruits.…”

“…The berry-derived precursor 1 is not abundant in nature, but it can be produced by bacterial cultivation via condensation of hydroxybenzaldehyde and acetone ( Feron et al, 2007 ). 2 is a secondary alcohol isolated originally from Taxus wallichiana ( Chattopadhyay et al, 2001 ).…”