Transcriptionally induced nucleoid-associated protein-like in combined-culture serves as a global effector of secondary metabolism.

Combined-cultures involving mycolic acid-containing bacteria (MACB) can stimulate secondary metabolite (SM) production in actinomycetes. In a prior investigation, we screened JCM4020 mutants with diminished production of SMs, specifically undecylprodigiosin (RED), which was enhanced by introducing the MACB TP-B0596. In this study, we conducted mutational analysis that pinpointed the gene, which we assigned the gene name (combined-culture related regulatory protein no. 1), as a crucial factor in the deficient phenotype observed in the production of various major SMs in A3(2). Notably, the Ccr1 (SCO1842) homolog was found to be highly conserved throughout the genome. Although Ccr1 lacked conserved motifs, in-depth examination revealed the presence of a helix-turn-helix (HTH) motif in the N-terminal region and a helicase C-terminal domain (HCTD) motif in the C-terminal region in some of its homologs. Ccr1 was predicted to be a nucleoid-associated protein (NAP), and its impact on gene transcription was validated by RNA-seq analysis that revealed genome-wide variations. Furthermore, RT-qPCR demonstrated that was transcriptionally activated in combined-culture with , which indicated that Ccr1 is involved in the response to bacterial interaction. We then investigated HEK616 in combined-culture, and the knockout mutant of the homolog displayed reduced production of streptoaminals and 5aTHQs. This finding reveals that the Ccr1 homolog in species is associated with SM production. Our study elucidates the existence of a new family of NAP-like proteins that evolved in species and play a pivotal role in SM production.