A promising chassis derived from Streptomyces sp. FR-008 and its development for polyketide derived natural products heterologous overproduction system

Polyketide nature products are one of the richest resources for both pharmacy industry and academic study. These well-known products play attractive bioactivities, such as antibiotic, antifungal, antitumor, immunosuppressant. Due to the long growth time and difficulty in genetic manipulation of the producer strain varies case by case, it’s worthy to construct an general host with sufficient precursor supply, no competition pathways, an easy cultivation and efficient conjugation system, as a general platform for polyketide efficient production.

In a large number of Streptomyces strains studied in our lab, Streptomyces sp. FR-008 shows great potential as a super host. Its excellent superiority exhibits mainly on fast growing and efficient conjugation system. Besides, it can naturally harbor a 130 kb PKS gene cluster and produce candicindin as final product in a relative high level. This implies its capability to hold, translate and modify large size of PKS proteins, then serve abundant precursors to be taken into PKS biosynthesis.

In our study, we tried to engineer this strain from two aspects, knockout all the PKS pathways and introducing crucial pathway or genes, in the hopes of finally developing a kit-like PKS heterologous overproduction system. The PacBio platform was applied for the genome sequencing project to get a complete genome. The genome size is only 7.1 Mb, which is one of the smallest among current sequenced Streptomyces genomes. in addition,  malonyl-CoA and methylmalonyl-CoA biosynthesis genes were intergrated on the host chromosome.