Background
The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing
Streptomyces lincolnensis
remain poorly understood.
Results
In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in
S. lincolnensis
. Deletion of
abrT
gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (
lin
) cluster genes and activated that of the morphological developmental genes
amfC
,
whiB
, and
ftsZ
. We demonstrated that AbrT bound to two motifs (5′-CGCGTACTCGTA-3′ and 5′-CGTACGATAGCT-3′) present in the bidirectional promoter between
abrT
and
SLCG_1980
genes. This consequently repressed
abrT
itself and its adjacent gene
SLCG_1980
that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to
abrT
-
SLCG_1980
intergenic region. Furthermore, based on functional analysis of the AbrT homologue in
Saccharopolyspora erythraea
, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes.
Conclusions
AbrT functions as a regulator for governing lincomycin production and morphological development of
S. lincolnensis
. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in
S. lincolnensis
. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12934-024-02498-8.
