Direct Cloning and Heterologous Expression of the Dmxorosin Biosynthetic Gene Cluster from Streptomyces thermolilacinus SPC6, a Halotolerant Actinomycete Isolated from the Desert in China

Streptomyces thermolilacinus SPC6 is a halotolerant strain isolated from the Linze Desert in China. It has a very high growth rate and short life cycle compared to other Streptomycetes, including the model organism Streptomyces coelicolor. The one strain-many compounds fermentation approach and global natural products investigation revealed that Streptomyces thermolilacinus SPC6 exhibits impressive productivity of secondary metabolites. Genome mining uncovered 20 typical secondary metabolic biosynthetic gene clusters (BGC), with a BGC dmx identified as completely silent. Subsequently, this cryptic BGC was successfully directly cloned and heterologously expressed in Streptomyces hosts, resulting in the discovery of a new lanthipeptide, dmxorosin. Notably, the proposed biosynthetic pathway indicates its potential as a basis for the synthetic biology of new lanthipeptide.