Heterologous expression of human interleukin-6 in Streptomyces lividans TK24 using novel secretory expression vectors

Streptomyces is an attractive host for heterologous protein secretion. To further optimize its expression capacity, better expression vectors will be helpful. Here, based on pSGL1, a high copy number plasmid present in Streptomyces globisporus C-1027, we constructed a series of novel E. coli-Streptomyces shuttle expression vectors pIMB2–4. These vectors, which are compatible with pIJ-derived vectors, contain the strong promoter ermE*p and signal sequence SPMelC1 of the first ORF of melanin operon in S. antibiotics (pIMB2), SPCagA of C-1027 apoprotein in S. globisporus C-1027 (pIMB3 and pIMB4). Using these vectors, human interleukin-6 (IL-6) could successfully be expressed and secreted using S. lividans TK24 as host. Furthermore, replacement of a rare leucine codon TTA with CTG in SPCagA enhanced IL-6 production.