A research led by Professor KIM Chu-Young from the Department of Biological Sciences in NUS has identified a key bacterial enzyme, Ecm18, involved in the production of the antibiotic drug echinomycin. Using a powerful X-ray beam, how this enzyme conducts its chemistry has been identified precisely.
Ecm18 is an enzyme from the soil bacterium Streptomyces lasaliensis that converts the disulfide bond found in the precursor molecule triostin A into a thioacetal bridge to form the final product echinomycin (see Figure 1). The enzyme structure, catalytic mechanism, and substrate specificity of Ecm18 has been reported in this research. The unique enzymatic chemical transformation is achieved by a combination of proximity effect, medium effect, and catalysis by strain.
Studying how nature synthesises these drugs can lead to the development of new methods for producing structurally complex drugs cheaply in the factory setting.
Figure 1 shows the X-ray crystal structure of Ecm18. [Image credit: Angewandte Chemie International Edition]
Figure 2 shows the conversion of triostin A into echinomycin by Ecm18. [Image credit: Angewandte Chemie International Edition]
Reference
Hotta K, Keegan RM, Ranganathan S, Fang M, Bibby J, Winn MD, Sato M, Lian M, Watanabe K, Rigden DJ, Kim CY. “Conversion of a Disulfide Bond to a Thioacetal Group during Echinomycin Biosynthesis”. Angewandte Chemie International Edition 53 (2014) 824
