INTRODUCTION ENZYMES: PENICILLIN G ACYLASE

Both 6-Aminopenicillanic acid (6-APA) and 7-Aminodeacetoxycephalosporanic acid (7-ADCA) are key intermediates used for the production of semi-synthetic Penicillins and Cephalosporins.

Some years ago 6-APA and 7-ADCA were predominantly produced by chemical means. This method was associated with a number of complex technical requirements, and used materials that caused environmental pollution as well as producing unwanted impurities in the product.

The Enzyme route, which is used as an alternative, provides many advantages over the chemical route that includes:

Reduced reaction time - increased operating efficiency
Specificity - the production of unwanted by-products is avoided and there is no need to extensively refine and purify the desired product
Cost saving - enzymes can be immobilized and therefore re-used several times, providing valuable cost savings
Environmentally friendly - enzymes are non corrosive and fully biodegradable




PRODUCT DESCRIPTION

The official nomenclature for Penicillin Acylase/Amidase (Enzyme) is E.C.3.5.1.11, and is derived from Escherichia coli.

Dalas Biotech has developed a method to produce Penicillin G Acylase on an industrial scale, that is free of -lactamase and other contaminants.




APPLICATION

The PENAM and CEPHAM class of -Lactam antibiotics, of Penicillins and Cephalosporins, are the most widely used antibiotics today.

The key intermediates 6-APA and 7-ADCA are obtained by the enzymatic deacylation of Penicillin G Potassium (Pen GK) and Cephalosporin G (Ceph G) respectively.

The enzymatic conversion is brought about by the cleavage of a side chain of the molecule, in a highly specific manner:







PRODUCT VARIATIONS


We have developed several versions of the Penicillin G Acylase enzyme in-house, as a result of the efforts of our research and development team. The two main versions do have their specific independent advantages, but share some similarities as well:

1. Black Enzyme
2. "Dalenz" White Enzyme


The Black Enzyme:
i. A well-established biocatalyst, successfully applied by many of our customers.
ii. Its key benefits lie in its significantly higher activity, and resistance to solvents.

Our latest development Dalenz:
i. The advantage of Dalenz over other biocatalysts lies in its stability - an attribute of its covalent bonding to a carrier.
ii. The Dalenz white enzyme combines both high specific activity, with unmatched stability of the catalyst under process conditions.




OPERATING PARAMETERS

Although enzymes provide a great number of advantages over chemicals, it is important to maintain certain conditions for the most efficient output. For the Dalas Penicillin G Acylase enzymes, we suggest the following:

Conditions Pen-G-K Ceph-G
1. Buffer Not Required Not Required
2. Temperature 30C to 38C 30C to 38C
3. Substrate Concentration 8.0 % 5.5 %
4. Loading Per Kg. of Enzyme
(Enzyme: Substrate)
1:1 1:1
5. Expected Reaction Time 80 minutes 80 minutes
6. Percentage Conversion
by HPLC
98% ▒ 0.5 97% ▒ 0.5
7. D.M. Water Quality Conductivity should be less Than 20 ÁS, and free from both Chlorides and Microbes.





SPECIFICATIONS

Black Enzyme
White Enzyme