Biocatalysis and Biotransformations

Research focus

The Peer review has evaluated this group as Good

The main need of that field of industrial chemistry dealing with biologically active substances (drugs, flavours, fragrances, insecticides, herbicides, food additives) is the optimisation of efficient methods for the synthesis of single enantiomers of chiral molecules. The authorities in charge of preserving human health and well-being are now suggesting to use the single biologically active enantiomers of chiral commercial compounds. There are two main catalytic approaches to the synthesis of enantiomerically pure compounds. The first one consists in the use enantiopure ligands to obtain chiral transition-metal complexes which are employed to catalyse certain types of chemical reactions. The second approach is based on biocatalysis, which takes advantage of those enzymes which are known to control the complex machine of living beings. Biocatalysis is known to be very versatile, especially in the identification of new procedures: a lot of isolated enzymes and/or microorganisms are available, accepting a wide range of substrates, yet working with high stereoselectivity. This research group has been a pioneer in the application of biocatalysis to organic synthesis since the beginning of the seventies. This group has employed enzymes in the synthesis of the single enantiomers of amino deoxysugars (to be used as antitumoural drugs), vitamins, pherormones, etc. As an evolution of the synthesis of pherormones, the group has acquired great skill in the biogeneration of flavours and in the enzyme -mediated synthesis of the single enantiomers of odorous molecules. The enantiopure stereoisomers of many chiral commercial fragrances have been prepared by enzyme-mediated procedures, and their odour properties have been evaluated by Givaudan perfumers. Relevant examples of enantioselectivity in the odour perception have been highlighted. This kind of investigation is strongly supported, as Corey has recently stated (J. AM. CHEM. SOC. 2006, 128, 1346-1352), by the interest in the problem of how humans are able to distinguish among so many odoriferous molecules and the availability of powerful new methods of synthesis…..with diastereoand enantio-control. The emphasis given to the mechanism of olfaction (Nobel Prize in Physiology or Medicine 2004 assigned to R. Axel and L. Buck "for their discoveries of odorant receptors and the organization of the olfactory system”) has promoted a lot of studies on the relationship between structure and “activity”, in this case odour response. This knowledge is far poorer than that regarding drugs and pharmacological activity (C.S Sell, Angewandte Chemie International Edition Volume 45, Issue 38, Pages: 6254-6261l) and it should be improved and exploited for the following purposes. The first one is the identification of the most odorous stereoisomers of chiral fragrances, which are currently commercialised as racemates, in order to reduce the amount of chemicals to be added in the products of fine and functional perfumery. The second one is the discovery of new powerful odorants through SAR techniques. In strict connection with this work on flavours and fragrances, the group has also developed isotopic methods for the authentication of the origin of flavours, in order to distinguish their extractive or synthetic origin. In this context, in the years of the human cases of BSE relevant studies have been performed on the biosynthesis of tyrosine in plants and animals. An isotopic method based on the evaluation of deltaO18 of the OH group of tyrosine gave information on the diet of animals, and allowed to distinguish the contribute of vegetal feeding. The combination of new synthetic techniques (e.g benzannulation) with enzyme - catalysed key steps has been exploited to prepare single enantiomers of chiral drugs and ligands. The work on drugs has been also enriched by studies on the structural identification of impurities contained in commercial drugs and strictly related to the employed synthetic procedures. Some components of the research group have devoted their interest to the enzyme-mediated synthesis of modified phospholipids of natural origin and non natural amino acids. They have isolated an enzyme with phospholipase D (PLD) activity which is at present the catalyst in probably the largest enzyme catalysed transformation in fine chemistry in Italy. Phosphatidyl serine is Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta” – Research Assessment Excercise 2003-2006 36 produced in ton scale with this enzyme. The 3D structure and the mechanism of this PLD have been elucidated and the protein cloned in E.coli. The activity in the field of amino acid secures the obtainement of non-natural amino acids of D- and L- configuration through enzymatic kinetic resolution or via deracemization by stereoinversion, in a process in which 5 different enzymes are employed in the same vessel. In this way a racemic amino acid is converted into the L-form in 100% yield. The research group is a reference point for relevant companies: Perfetti van Melle (n. 3 in the world in the field of confectionery), Mastertaste (n.10 in the world in the field of flavours and fragrances), Robertet (n. 11 in the world in the field of flavours and fragrances), Chemi, Flamma and others.

Departments

Dipartimento di Chimica, Materiali e Ingegneria Chimica

Professors

Full Professors
Claudio Fuganti
Stefano Servi
Associate Professors
Maria Elisabetta Brenna
Assistant Professors Paola D’Arrigo
Francesco Gilberto Gatti
Orso Vajna de Pava