Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynt
- PDF / 2,813,205 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 61 Downloads / 165 Views
Microbial Cell Factories Open Access
RESEARCH
Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynthesis Chun‑Yan Lin1, Ai‑Ping Pang1,3, Yue Zhang1,4, Jianjun Qiao1,2 and Guang‑Rong Zhao1,2*
Abstract Background: Lincomycin, produced by Streptomyces lincolnensis, is a lincosamide antibiotic and widely used for the treatment of the infective diseases caused by Gram-positive bacteria. The mechanisms of lincomycin biosynthesis have been deeply explored in recent years. However, the regulatory effects of LmbU that is a transcriptional regulator in lincomycin biosynthetic (lmb) gene cluster have not been fully addressed. Results: LmbU was used to search for homologous LmbU (LmbU-like) proteins in the genomes of actinobacteria, and the results showed that LmbU-like proteins are highly distributed regulators in the biosynthetic gene clusters (BGCs) of secondary metabolites or/and out of the BGCs in actinomycetes. The overexpression, inactivation and complementation of the lmbU gene indicated that LmbU positively controls lincomycin biosynthesis in S. lincolnensis. Comparative transcriptomic analysis further revealed that LmbU activates the 28 lmb genes at whole lmb cluster man‑ ner. Furthermore, LmbU represses the transcription of the non-lmb gene hpdA in the biosynthesis of l-tyrosine, the precursor of lincomycin. LmbU up-regulates nineteen non-lmb genes, which would be involved in multi-drug flux to self-resistance, nitrate and sugar transmembrane transport and utilization, and redox metabolisms. Conclusions: LmbU is a significant pleiotropic transcriptional regulator in lincomycin biosynthesis by entirely activat‑ ing the lmb cluster and regulating the non-lmb genes in Streptomyces lincolnensis. Our results first revealed the pleio‑ tropic regulatory function of LmbU, and shed new light on the transcriptional effects of LmbU-like family proteins on antibiotic biosynthesis in actinomycetes. Keywords: Streptomyces lincolnensis, Lincomycin, LmbU, Transcriptional regulator, Pleiotropic regulation Background Streptomycetes are famous for the ability to produce a great variety of valuable secondary metabolites, which have pharmacological activities such as antibacteria, antifungi, antiparasites, anticancer, and immunosuppression [1]. Genes encoding for biosynthesis of secondary
*Correspondence: [email protected] 1 Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, China Full list of author information is available at the end of the article
metabolites are usually located together into the biosynthetic gene clusters (BGCs) in streptomycetes. For timely and coordinated expression, BGCs are under strict controls at the transcription level of intertwined regulation by pleiotropic regulators and pathway specific regulators [2]. The pathway specific regulators encoded by genes i
Data Loading...
