Challenges of functional expression of complex polyketide biosynthetic gene clusters.

Polyketide natural products are valuable sources of bioactive molecules such as nutraceuticals and pharmaceuticals. The tremendous development of the genome sequence database revealed that the majority of the biosynthetic gene clusters (BGCs) are cryptic. Activation of these cryptic BGCs and identification of the related products is essential for finding more lead compounds for pharmaceuticals. On the other hand, 99% of microbes in nature cannot be cultured in regular conditions, which greatly hinders the efforts to explore their biosynthetic potentials. Expression of polyketide BGCs in heterologous hosts with better growth, good genetic characteristics, and amenable molecular tools is a robust approach to identify new polyketides and characterize their biosynthesis. This review outlines the challenges in the heterologous production of polyketide BGCs of bacterial origins.