Micro-organisms could be employed to make drugs that are too complicated to synthesise chemically, say UK chemists.

Greg Challis and colleagues at Warwick University say feeding bacteria with simple synthetic precursors of a required product could avoid the need for complex organic syntheses.

The bacteria Streptomyces coelicolor naturally produce antibiotics called prodiginines. Challis's team fed precursors of prodiginine molecules to mutant S. coelicolor bacteria that had been genetically engineered to be deficient in certain enzymes.   Depending on whether or not the bacteria produced the expected prodiginines the researchers could identify which enzymes were involved in various stages of the synthetic pathway.

Challis said these precursor feeding experiments could also be used to make the bacteria produce analogues of the natural prodiginines. 'This combines the strength of organic synthesis, to produce large numbers of analogues of structurally simple precursors, with the synthetic power of biology, to assemble highly complex and synthetically difficult structures,' he said.

Challis stressed the need for further understanding of the biosynthetic pathway to determine which precursor analogues will work, but he added, 'this approach will be particularly valuable for generating analogues of streptorubin B [a prodiginine] which are difficult to access using current synthetic approaches.'

'In the future, we envisage that other biosynthetic pathways to complex natural products will be elucidated using similar types of approaches,' said Challis.

Michael Smith