Efficient ilamycins production utilizing Enteromorpha prolifera by metabolically engineered Streptomyces atratus

Background: With the invasion of green tides and the increase of urban green areas worldwide, multimillion tons of Enteromorpha need to be reutilized. Ilamycins, novel cyclic heptapeptides with significant anti-TB activities, are isolated from Streptomyces atratus SCSIO ZH16, a deep-sea-derived strain. It is crucial to develop an efficient production process that can utilize inexpensive nitrogen sources to achieve massive production of ilamycins. Results In this study, Enteromorpha prolifera powder is considered a promising biomass resource for the production of commercial chemical products production. By using E. prolifera powder as a nitrogen source, the production of ilamycins reached 709.97 mg/L through optimization of the nitrogen source using the engineered strain S. atratus SCSIO ZH16 Δ R . After mutant strain constructions and tests, S. atratus SCSIO ZH16 Δ R bldD was found to be a more suitable strain for utilizing E . prolifera powder. Furthermore, the production titer of ilamycins and ilamycin E reached 1561.77 mg/L and 745.44 mg/L, respectively, in a 5-L bioreactor. Conclusions This study suggests that E. prolifera is a promising and eco-friendly nitrogen source for the production of ilamycins. Engineered strain S. atratus SCSIO ZH16 Δ R bldD was found to be a more suitable strain for utilizing E . prolifera powder.