Development of Spectinabilin Over-Producing Mutant Streptomyces sp. S-N87 having Nematicidal Activities

Abstract

Abstract Spectinabilin (neoaureothin) is a rare nitrophenyl-substituted polyketide produced by some Streptomyces species. This compound is known to exhibit various biological activities such as anticancer, antibiotic, immunomodulatory, antimalarial and nematicidal effects. Despite being a valuable secondary metabolite for the development of novel drugs, the production yield of spectinabilin is < 200 mg/litre at the current level. To improve the yields of this promising compound without biosafety and regulation issues, this study conducted traditional mutagenesis. A total of 1,025 mutants were generated under high mortality conditions by NTG (N-methyl-N’-nitro-N-nitrosoguanidine) from parental strain Streptomyces sp. AN091965. One of the mutants, S-N87 showed up to about 10-fold spectinabilin productivity (354.8 ± 7.8 mg/L) compared to the parental strain Streptomyces sp. AN091965 (37.6 ± 5.6 mg/L) in flask culture conditions, representing the highest spectinabilin yield reported thus far. In addition, this strain showed a stable yield of 2.27 g/L even in a scaled-up environment (150 L tank fermentation), which suggests that the selected mutant is a genetically stable and robust strain. Further, the mutant Streptomyces sp. S-N87 that enhanced spectinabilin production stably showed a significant increase in nematicidal activities against pine wilt nematode compared to the parental strain. The present study is the first to develop a Streptomyces mutant that over-produces spectinabilin by traditional mutagenesis. Further studies such as whole-genome analysis and genetic modification are needed to provide a theoretical basis and insights into the polyketide synthase pathway of this talented mutant.