Streptomyces is the largest genus of Actinobacteria and the main producer of natural antibiotics used in clinical treatment, which makes Streptomyces an interesting tool to combat the increase of antibiotic resistant bacteria. Streptomyces spp. have large genomes with several biosynthetic gene clusters (BGCs), but most of them are cryptic under laboratory conditions [1]. This secondary metabolism is strictly regulated by regulatory cascades, so it is important to understand this regulatory network to discover new molecules and enhance their production [2].
Typical two-component systems are composed by a histidine kinase (HK) and a response regulator (RR) and they play a crucial role in antibiotic regulation. Several of them have been studied in the model organism S. coelicolor [3] and among them the orphan RR Aor1 is a key regulator that controls several genes of secondary metabolism, including some cryptic BGCs [4].
As an orphan RR, the HK related to Aor1 remains unknown. By bioinformatic prediction, the HKs encoded by the genes SCO3750 and SCO6424 seem to be the partners of Aor1. In this work, we study the deletion mutants of these genes and their similarity with the Δaor1 phenotype. Our objective is to unravel the signals that control Aor1 to better understand how antibiotic production is regulated in Streptomyces.
The Δ3750 mutant presents a delay of differentiation on LB, like the Δaor1 mutant, and the same phenotype as Δaor1 on YEPD. On the contrary, the Δ6424 mutant does not have any similarity with Δaor1. These results suggest that SCO3750 is the HK that controls Aor1.
References:
- Donald, L. et al. Res. 2022, 13, 418–465.
- Xia H. et al. Microbiol. 2020, 11:406.
- Sánchez de la Nieta, R. et al. J. Mol. Sci. 2022, 23, 15085.
- Antoraz S. et al. Microbiol. 2017, 8:2444.
