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Biosynthesis of GE2270 and derivatives in Nonomuraea

Biosynthesis of GE2270 in a strain of Nonomuraea bacteria could lead to the development of improved methods for synthesizing the thiopetide macrocycle and creating derivatives. GE2270 and its derivatives have potent activity against Gram-positive bacteria, but the bacteria that produces it, Planobispora rosea, is not amenable to genetic manipulation. The P. rosea gene cluster responsible for GE2270 synthesis was expressed in a strain of Nonomuraea that is amenable to genetic manipulation. In the transgenic Nonomuraea strain, manipulation of the GE2270 gene cluster resulted in the generation of four fully cyclized GE2270 variants. Next steps could include generating additional GE2270 variants and optimizing their potency and pharmacokinetic properties.

SciBX 6(34); doi:10.1038/scibx.2013.937
Published online Sept. 5, 2013

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Tocchetti, A. et al. Chem. Biol.; published online Aug. 8, 2013;
Contact: Margherita Sosio, Naicons scarl, Milan, Italy