A bacterium is a microscopic chemical factory producing antibiotics, immunosuppressants, and anticancer drugs no chemist can synthesize, according to chemical engineer Camilla Kao. Its products are all made for the benefit of the bacterium itself, but pharmaceutical companies have been tapping into microbial drug manufacturing for some time.

	Camilla Kao

However, although some processes are very successful, using bacteria to make drugs involves slow and costly cultivation of suitable bacteria. Now, Kao and her colleagues at Stanford University are hoping to manipulate bacteria to "overproduce" useful compounds such as antibiotics. "Companies have proprietary mutant [bacterial] strains that have been worked on for more than twenty years," she explains, "but many of the mutations are still unknown."

Saccharopolyspora erythraea

Kao is "reverse engineering" many of these mutants to expose what changes have occurred in the proprietary overproducers with the aim of making new mutant strains to synthesize other drugs. She investigated the bacterial species, Saccharopolyspora erythraea which produces erythromycin, an antibiotic for chest infections at ten times the rate of the wild-type strain using DNA microarrays. These revealed that the useful changes lie not in the cluster of genes known to produce the antibiotic but in a mutation of another gene that co-regulates the timing of expression for the antibiotic-producing genes. With this mutation the bacterium produces erythromycin for five days instead of the usual one day.

The research provides an important new clues as to how to engineer other mutant strains to overproduce different antibiotics. "With knowledge of how bacteria work as chemical factories, in a short time we should be able to engineer high producers that are equivalent to twenty years of work with the traditional method," Kao said.

http://chemeng.stanford.edu/01About_the_Department/03Faculty/Kao/kao.html