[ABC transporter SgnA/B promotes extracellular transport and efficient production of natamycin]

Natamycin is a natural, broad spectrum and highly efficient antifungal compound that belongs to polyene macrolide antibiotics. It has been used in prevention of food fungal contamination and treatment of clinical fungal infection. The extracellular transport efficiency of natamycin may be an important factor hampering the yield of natamycin produced by Streptomyces gilvosporeus. The extracellular transporter SgnA/B of natamycin was analyzed by bioinformatics tools and molecular docking techniques. This ATP-binding cassette transporter, consisted of SgnA and SgnB, is a heterodimers with inward-facing conformation. The difference between the natamycin combining efficiency of the two drug-binding cavities in SgnA/B is favorable for natamycin extracellular transport. sgnA/B gene was overexpressed in S. gilvosporeus F607 and the effects of sgnA/B gene overexpression on natamycin synthesis and extracellular transport were analyzed. In F-EX strain, the extracellular/intracellular ratio of natamycin in logarithmic synthesis stage was increased, and the total fermentation yield at 120 h was increased by 12.5% and reached to 7.38 g/L. Moreover, transcriptome sequencing analysis showed that sgnA/B gene overexpression affected the expression of genes involved in the metabolism of various amino acids, propionate, glucose, C5-branched dibasic acid and TCA cycle. This research demonstrated that the enhanced extracellular transport increased the synthesis of natamycin by S. gilvosporeus, and S. gilvosporeus F-EX showed good potential for the industrial production of natamycin.