Characterization of an Lrp/AsnC family regulator SCO3361, controlling actinorhodin production and morphological development in Streptomyces coelicolor
Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction in actinorhodin (Act) production and delay in aerial mycelium formation and sporulation on solid media. Dissection of the mechanism underlying the function of SCO3361 in Act production revealed that it altered the transcription of the cluster-situated regulator gene actII-ORF4 by directly binding to its promoter. SCO3361 was an auto-regulator and simultaneously activated the transcription of its adjacent divergently transcribed gene SCO3362. SCO3361 affected aerial hyphae formation and sporulation of S. coelicolor by activating the expression of amfC, whiB, and ssgB. Phenylalanine and cysteine were identified as the effector molecules of SCO3361, with phenylalanine reducing the binding affinity, whereas cysteine increasing it. Moreover, interactional regulation between SCO3361 and SACE_Lrp was discovered for binding to each other’s target gene promoter in this work. Our findings indicate that SCO3361 functions as a pleiotropic regulator controlling secondary metabolism and morphological development in S. coelicolor.
KeywordsLrp/AsnC family Streptomyces coelicolor SCO3361 Act production Morphological development Interactional regulation
This work was supported by the National Program on Key Basic Research Project (973 program, 2013CB734000), the National Natural Science Foundation of China (Grant Nos. 31300081, 31570074, 31600064), the Anhui Provincial Natural Science Foundation (Grant No. 1708085QC49), and the Initial Foundation of Doctoral Scientific Research in Anhui University (01001904, J01001935).
Compliance with ethical standards
This article does not contain any studies with human participants or animals performed by any of the authors.
The authors declare that they have no competing interests.
- Chong PP, Podmore SM, Kieser HM, Redenbach M, Turgay K, Marahiel M, Hopwood DA, Smith CP (1998) Physical identification of a chromosomal locus encoding biosynthetic genes for the lipopeptide calcium-dependent antibiotic (CDA) of Streptomyces coelicolor A3(2). Microbiology 144(Pt 1):193–199CrossRefPubMedGoogle Scholar
- Davis NK, Chater KF (1992) The Streptomyces coelicolor whiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation. Mol Gen Genomics 232(3):351Google Scholar
- Gao C, Hindra, Mulder D, Yin C, Elliot MA (2011) Crp is a global regulator of antibiotic production in Streptomyces. MBio 3(6):17–17Google Scholar
- Jeong Y, Kim J-N, Kim MW, Bucca G, Cho S, Yoon YJ, Kim B-G, Roe J-H, Kim SC, Smith CP, Cho B-K (2016) The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2). Nat Commun 7:11605. doi:10.1038/ncomms11605 CrossRefPubMedPubMedCentralGoogle Scholar
- Kieser T, Bibb MJ, Buttner MJ, Charter KF, Hopwood DA (2000) Practical Streptomyces genetics. John Innes Foundation, NorwichGoogle Scholar
- Mo S, Sydor PK, Corre C, Alhamadsheh MM, Stanley AE, Haynes SW, Song L, Reynolds KA, Challis GL (2008) Elucidation of the Streptomyces coelicolor pathway to 2-undecylpyrrole, a key intermediate in undecylprodiginine and streptorubin B biosynthesis. Chem Biol 15(2):137–148CrossRefPubMedGoogle Scholar
- Nett M, Ikeda H, Moore BS (2009) Genomic basis for natural product biosynthetic diversity in the Actinomycetes. Nat Prod Rep 26(11):1362–1384Google Scholar
- Rigali S, Nothaft H, Noens EE, Schlicht M, Colson S, Müller M, Joris B, Koerten HK, Hopwood DA, Titgemeyer F, van Wezel GP (2006) The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR-family regulator DasR and links N-acetylglucosamine metabolism to the control of development. Mol Microbiol 61(5):1237–1251Google Scholar
- Romero DA, Hasan AH, Lin Y-f, Kime L, Ruiz-Larrabeiti O, Urem M, Bucca G, Mamanova L, Laing EE, van Wezel GP, Smith CP, Kaberdin VR, McDowall KJ (2014) A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing. Mol Microbiol 94(5):963–987Google Scholar
- Sprusansky O, Stirrett K, Skinner D, Denoya C, Westpheling J (2005) The bkdR gene of Streptomyces coelicolor is required for morphogenesis and antibiotic production and encodes a transcriptional regulator of a branched-chain amino acid dehydrogenase complex. J Bacteriol 187(2):664–671Google Scholar
- Wezel GPV, Mcdowall KJ (2011) The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 28(7):1311–1333Google Scholar
- Wilkinson CJ, Hughes-Thomas ZA, Martin CJ, Böhm I, Mironenko T, Deacon M, Wheatcroft M, Wirtz G, Staunton J, Leadlay PF (2002) Increasing the efficiency of heterologous promoters in Actinomycetes. J Mol Microbiol Biotechnol 4(4):417–426Google Scholar