Physicochemical Studies of L-Asparaginase from Erwinia carotovora

Abstract

SOME L-asparaginases (L-asparagine amidohydrolase, EC 3.5.1.1) are able to destroy asparagine dependent tumours in animals and bring about regression in some cases of acute lymphatic leukaemia in man¹. The anti-tumour property of this enzyme was first recognized by Broome² with the asparaginase from guinea-pig serum and has since been observed with the enzyme from chicken liver³. Most of the clinical work, however, has been carried out with the more readily available asparaginases from bacteria. An asparaginase from Escherichia coli⁴, and more recently the enzyme from Erwinia carotovora⁵, are both being used in clinical trials on leukaemia. One interesting aspect of the clinical use of asparaginases is that not all preparations are effective against tumours. For example, the enzymes from guinea-pig liver⁶. Bacillus coagulans⁴ and yeast⁷ are ineffective. In fact, only one of the two asparaginases present in E. coli exhibits this property. Furthermore, those which are effective differ in their efficacy towards the 6H3HED tumour in mice which is normally used for the assessment of anti-tumour activity. Information on molecular structure may shed light on those features of the asparaginase which confer this property and suggest ways of enhancing it.