Bacteria being used to make anticancer agents could provide an extra source of lead compounds for the pharmaceutical industry, say European researchers. Barrie Wilkinson of Biotica, a UK biotechnology company, and co-workers have used genetically engineered strains of the bacterium Streptomyces parvulus to produce compounds that selectively inhibit growth of human cancer cells.

Streptomyces parvulus naturally produces a compound called borrelidin. Borrelidin is an effective inhibitor of angiogenesis, a key process in the spread of malignant tumours. Wilkinson's team engineered strains of the bacteria that cannot make borrelidin unless the correct starting material is added. The team used these strains to prepare biologically active analogues of borrelidin by incubating the strains with alternative starting materials. They tested the cytotoxicities of the borrelidin analogues and found that some showed selectivity against selected cancer cell lines.

According to the researchers, this strategy could help make novel biologically active compounds that are hard to prepare by traditional synthesis. 'This work paves the way for the use of these materials in semi-synthesis,' said Wilkinson. 'I hope that our efforts will help to keep natural products in the picture as a fantastic source of lead structures for the biotechnology and pharmaceutical industry.'

Tom Simpson of the University of Bristol, UK, commented on the work. The scope for this enzyme manipulation approach to produce novel analogues of parent bioactive molecules is becoming increasingly understood, he said. 'Detailed studies of this type are helping to build up a clearer picture of what can and cannot be achieved.'

Rebecca Gillan