Effects of pigment gene deletions on validamycin A production in Streptomyces hygroscopicus var. jinggangensis

Abstract:

[Objective] We studied the contributions of four pigment biosynthetic genes to validamycin A yield, biomass accumulation, and the color of fermentation broth via individual gene deletions.[Methods] The deletion mutants were obtained via homologous recombination. The titer of validamycin A was detected by HPLC. The transcription of validamycin biosynthetic genes was quantified by qRT-PCR, and the growth was measured with dry cell weight.[Results] Compared with the parent strain, the deletion of DOPA melanin genes increased the validamycin A titer from 20.6 to 23.1 g/L (by 12%), whereas the deletion of type Ⅲ polyketide synthase melanin genes showed no effect. The inactivation of type Ⅱ polyketide synthase spore pigment genes and ochronotic pigment genes decreased validamycin A production by 11.7% and 17.2%, respectively. All these mutant strains had no significant change in transcriptional level and the color of supernatant.[Conclusion] Pigment biosynthetic gene deletions showed different effects on validamycin yield and biomass accumulation, and the deletion of DOPA melanin biosynthetic genes redirected the precursor flux and successfully increased the yield of validamycin A.