TY - JOUR
T1 - MacRS controls morphological differentiation and natamycin biosynthesis in Streptomyces gilvosporeus F607
AU - Zong, Gongli
AU - Cao, Guangxiang
AU - Fu, Jiafang
AU - Zhang, Peipei
AU - Chen, Xi
AU - Yan, Wenxiu
AU - Xin, Lulu
AU - Zhang, Wenchi
AU - Xu, Yan
AU - Zhang, Rongzhen
N1 - Funding Information:
This work was supported by the National Key Research and Development Program of China [China, grant number 2018YFA0900302 , 2018]; the National Science Foundation of China [China, grant number 31970045 , 2021]; the Academic Promotion Programme of Shandong First Medical University [China, grant number LJ001 , 2019]; the National First-class Discipline Program of Light Industry Technology and Engineering [China, grant number LITE2018-12 , 2018]; and the Program of Introducing Talents of Discipline to Universities [China, grant numbers 111-2-06 , 2020].
Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - Streptomyces gilvosporeus F607 produces large amounts of natamycin in a process regulated by multiple networks, including two-component systems (TCSs). The macR and macS genes, which are annotated as rs12540 and rs12545, respectively, in S. gilvosporeus F607, affect natamycin biosynthesis and sporulation. The findings of this study indicate that deletion of macRS from S. gilvosporeus F607 prevents the production of natamycin, delays spore formation (according to scanning electron microscopy), and results in aerial hyphae lacking compartments separated by septa (according to transmission electron microscopy). Real-time quantitative polymerase chain reaction (RT-qPCR) analyses revealed that the expression levels of natamycin biosynthesis-related genes and genes essential for septum formation during sporulation were affected in the ΔmacRS mutant strain. Molecular simulations and electrophoretic mobility shift assays (EMSAs) suggested MacR not only interacted with the intergenic region of sgnM and sgnR, but also with the promoter of penicillin-binding protein gene ftsL required for cell division. sgnR promoter was presumed to be the binding target of MacR based on the RT-qPCR results. MacR had different affinity with two binding sites: one was located at ftsL promoter region with a perfect inverted repeats ‘TGAGTACGCGTACTCA’, the other was located at the presumed sgnR promoter with an imperfect inverted repeats ‘TGAAGGTGCTGGACTCA’. We propose a hypothesis of a three-level regulatory pathway based on pleiotropic transcriptional regulator MacR and its target genes sgnR and ftsL; the pathway activates natamycin biosynthesis and influences septum development via direct and indirect effects in S. gilvosporeus F607.
AB - Streptomyces gilvosporeus F607 produces large amounts of natamycin in a process regulated by multiple networks, including two-component systems (TCSs). The macR and macS genes, which are annotated as rs12540 and rs12545, respectively, in S. gilvosporeus F607, affect natamycin biosynthesis and sporulation. The findings of this study indicate that deletion of macRS from S. gilvosporeus F607 prevents the production of natamycin, delays spore formation (according to scanning electron microscopy), and results in aerial hyphae lacking compartments separated by septa (according to transmission electron microscopy). Real-time quantitative polymerase chain reaction (RT-qPCR) analyses revealed that the expression levels of natamycin biosynthesis-related genes and genes essential for septum formation during sporulation were affected in the ΔmacRS mutant strain. Molecular simulations and electrophoretic mobility shift assays (EMSAs) suggested MacR not only interacted with the intergenic region of sgnM and sgnR, but also with the promoter of penicillin-binding protein gene ftsL required for cell division. sgnR promoter was presumed to be the binding target of MacR based on the RT-qPCR results. MacR had different affinity with two binding sites: one was located at ftsL promoter region with a perfect inverted repeats ‘TGAGTACGCGTACTCA’, the other was located at the presumed sgnR promoter with an imperfect inverted repeats ‘TGAAGGTGCTGGACTCA’. We propose a hypothesis of a three-level regulatory pathway based on pleiotropic transcriptional regulator MacR and its target genes sgnR and ftsL; the pathway activates natamycin biosynthesis and influences septum development via direct and indirect effects in S. gilvosporeus F607.
KW - Cluster-situated regulatory factor
KW - MacRS two-component system
KW - Morphological differentiation
KW - Natamycin biosynthesis
KW - Septum formation
KW - Streptomyces. gilvosporeus
UR - http://www.scopus.com/inward/record.url?scp=85131461480&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131461480&partnerID=8YFLogxK
U2 - 10.1016/j.micres.2022.127077
DO - 10.1016/j.micres.2022.127077
M3 - Article
C2 - 35688098
AN - SCOPUS:85131461480
SN - 0944-5013
VL - 262
JO - Microbiological Research
JF - Microbiological Research
M1 - 127077
ER -