Chemo-enzymatic

Industrial production of amino acids by fermentation and chemo-enzymatic methods... 

In this chapter we consider amino acid production by fermentation and by chemo-enzymatic methods. We first consider the stereochemistry of amino adds and the importance of chirality in chemical synthesis. General approaches to amino add fermentation and recovery of amino adds from fermentation broths are then dealt with, followed by a detailed consideration of the production of L-phenylalanine by direct fermentation. Later in this chapter, chemo-enzymatic methods of amino acid... 

Two appendices are included at the end of this chapter. The first is intended to serve as a reminder, for those of you who might need it, of the nomendature and representation of stereoisomers. The second appendix contains descriptions of various chemo-enzymatic methods of amino acid production. This appendix has been constructed largely from the recent primary literature and includes many new advances in the field. It is not necessary for you to consult the appendix to satisfy the learning objectives of the chapter, rather the information is provided to illustrate the extensive range of methodology assodated with chemo-enzymatic approaches to amino add production. It is therefore available for those of you who may wish to extend your knowledge in this area. Where available, data derived from die literature are used to illustrate methods and to discuss economic aspects of large-scale production. 

SAQ 8.7 The product value at 100% capadty will now be (total cost of production + 7 to 15% ROD, ie 16.04 to 1654 + 1.12 to 2.48. So the minimum product value will be 17.16 per kg of L-phenylalanine and the maximum product value 19.02 per kg of L-phenylalanine. It is rattier difficult to say whether this fictitious process would survive or could compete. Actual data are absolutely necessary. On the other hand this exercise gives us a better understanding of process economics and can also be used to compare a fermentative process for the production of amino adds with, for example, a chemo-enzymatic process. Calculate the return on investment over a 15 year period for an amino add fermentation, based on the following data and assumptions. Production capadty = 500 tonnes per annum Selling price of product = 50 kg Cost price of product = 24.5 kg 1 Capital = 40 million Taxes = 50%. Assumptions Cost of dealer discount, distribution and freight = 20% total sales Startup costs = 10% of capital Working capital = 25% of net sales Administration plus R and D costs = 12.5% of net sales. 

Chemo-enzymatic epoxidation of unsaturated fatty acids with aqueous H2O2 has been conducted with considerable success and here we have a remarkable situation that undesirable ring opening of the epoxide does not occur. Excellent activity and stability has been realized with Novozym 435, a Candida antartica lipase B immobilized on polyacryl. This enzyme is readily separable, can be used several times without loss of activity, and has a turnover of more than 2,00,000 moles of products per mole of catalyst (Bierman et al., 2000). 

The reduction of a-hydroxynitriles to yield vicinal amino alcohols is conveniently accomplished with complex metal hydrides for example, lithium aluminum hydride or sodium borohydride [69]. However, it is still worth noting that a two-step chemo-enzymatic synthesis of (R)-2-amino-l-(2-furyl)ethanol for laboratory production was developed followed by successful up-scaling to kilogram scale using NaBH4/CF3COOH as reductant [70],... 

Padhi, S.K., Kaluzna, I.A., Buisson, D. et al. (2007) Reductions of cyclic beta-keto esters by individual Saccharomyces cerevisiae dehydrogenases and a chemo-enzymatic route to (lR,2S)-2-methyl-l-cyclohexanol. Tetrahedron Asymmetry, 18 (18), 2133-2138. 

D Arrigo, P, Lattanzio, M., Fantoni, P. and Servi, S. (1998) Chemo-enzymatic synthesis of the active enantiomer of the anorressant 2-benzylmorpholine. Tetrahedron Asymmetry, 9, 4021 -026. 

Apart from the energy savings, large amounts of reagents and solvents could be omitted by this chemo-enzymatic-fermentative cephalexin route ... 

Taylor, S.J.C., Sutherland, A.G., Lee, C., Wisdom, R., Thomas, S., Roberts, S.M. and Evans, C., Chemoenzymatic synthesis of (—)-carhovir utilizing a whole cell catalysed resolution of 2-azabicyclo[2.2.1 ]hept-5-en-3-one. J. Chem. Soc. Chem. Commun., 1990, 1120-1121 Evans, C.T., Roberts, S.M., Shoheru, K.A. and Sutherland, A.G., Potential use of carbocyclic nucleosides for the treatment of AIDS chemo-enzymatic syntheses of the enantiomers of carbovir. J. Chem. Soc. Perkin Trans. 1,1992, 589-592. 

Gu, R.-L., Lee, I.S. and Sih, C.J., Chemo-enzymatic asymmetric synthesis of amino acids. Enantioselective hydrolyses of 2-phenyl-oxazolin-5-ones. Tetrahedron Lett., 1992, 33, 1953-1956 Crich, J., Brieva, R., Marquart, P., Gu, R.-L., Flemming, S. and Sih, C.J., Enzymic asymmetric synthesis of a-amino acids. Enantioselective cleavage of 4-substituted oxazolin-5-ones and thiazolin-5-ones. J. Org. Chem., 1993, 58, 3252-3258. 

Dynamic kinetic resolution (DKR) is a process in which the resolution process is coupled with in situ racemization of unreacted substrate. This has been shown to be a potential and feasible method to produce 100 % theoretical yield. We have developed a chemo-enzymatic DKR to obtain higher desired yield for (5)-ibuprofen. The combined base catalyst with lipase has resulted in high conversion and excellent ee of the product. 

Orru, R.V.A., Mayer, S.F., Kroutil, W. and Faher, K., Tetrahedron, Chemoenzymatic deracemi-sationof (+)-2,2-disubstituted oxiranes. 1998, 54, 859. Steinreiber, A., Hellstrdm, H., Mayer, S.F., Orru, R.V.A., Faber, K., Chemo-enzymatic enantio-convergent synthesis of C4-huilding blocks containing a fully substituted chiral carbon center using bacterial epoxide hydrolases. Synlett, 2001, 111. 

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