WblA_ch, a Pivotal Activator of Natamycin Biosynthesis and Morphological Differentiation in Streptomyces chattanoogensis L10, Is Positively Regulated by AdpA_ch

Abstract

bDetailed mechanisms of WhiB-like (Wbl) proteins involved in antibiotic biosynthesis and morphological differentiation are poorly understood. Here, we characterize the role of WblA ch , a Streptomyces chattanoogensis L10 protein belonging to this superfamily. Based on DNA microarray data and verified by real-time quantitative PCR (qRT-PCR), the expression of wblA ch was shown to be positively regulated by AdpA ch . Gel retardation assays and DNase I footprinting experiments showed that AdpA ch has specific DNA-binding activity for the promoter region of wblA ch . Gene disruption and genetic complementation revealed that WblA ch acts in a positive manner to regulate natamycin production. When wblA ch was overexpressed in the wild-type strain, the natamycin yield was increased by ϳ30%. This provides a strategy to generate improved strains for natamycin production. Moreover, transcriptional analysis showed that the expression levels of whi genes (including whiA, whiB, whiH, and whiI) were severely depressed in the ⌬wblA ch mutant, suggesting that WblA ch plays a part in morphological differentiation by influencing the expression of the whi genes.

wblA , a pleiotropic regulatory gene modulating morphogenesis and daptomycin production in Streptomyces roseosporus

“…Similar results were observed in other groups who investigate the mechanisms underlying wblA regulating antibiotic production in streptomyces (Geiman et al 2006;Lee et al 2010;Yu et al 2014). It was shown that Wbl proteins may change their regulatory function in response to dormancy signals, including O 2 and nitric oxide (NO), via their iron-sulphur cluster (Nguyen et al 2006).…”

“…; Yu et al . ). It was shown that Wbl proteins may change their regulatory function in response to dormancy signals, including O 2 and nitric oxide (NO), via their iron‐sulphur cluster (Nguyen et al .…”

“…In addition, wblA positively regulates natamycin biosynthesis in S. chattanoogensis L10 (Yu et al . ). However, little is known about the function of wblA in S. roseosporus .…”

“…Recently, it was found that inactivation of wblA could activate the cryptic secondary metabolic gene clusters in S. ansochromogenes 7100 (Lu et al 2015) and S. somaliensi SCSIO ZH66 (Huang et al 2016). In addition, wblA positively regulates natamycin biosynthesis in S. chattanoogensis L10 (Yu et al 2014). However, little is known about the function of wblA in S. roseosporus.…”

The Application of Regulatory Cascades in Streptomyces: Yield Enhancement and Metabolite Mining

“…As a global repressor, WblA affects doxorubicin (DXR), tautomycetin, and daptomycin biosynthesis in their natural host strains Nah et al, 2012;Kim et al, 2014). However, WblA activates natamycin biosynthesis in Streptomyces chattanoogensis (Yu et al, 2014).…”