한빛사 논문
Soonkyu Hwang1,2, Namil Lee1,2, Yujin Jeong1,2, Yongjae Lee1,2, Woori Kim1,2, Suhyung Cho1,2, Bernhard O. Palsson3,4,5 and Byung-Kwan Cho1,2,6,*
1 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea, 2 KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea, 3 Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA, 4 Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA, 5 Novo Nordisk Foundation Center for Biosustainability, 2800 Kongens Lyngby, Denmark and 6 Intelligent Synthetic Biology Center, Daejeon 34141, Republic of Korea
*To whom correspondence should be addressed.
Abstract
Determining transcriptional and translational regulatory elements in GC-rich Streptomyces genomes is essential to elucidating the complex regulatory networks that govern secondary metabolite biosynthetic gene cluster (BGC) expression. However, information about such regulatory elements has been limited for Streptomyces genomes. To address this limitation, a high-quality genome sequence of β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27 064 is completed, which contains 7163 newly annotated genes. This provides a fundamental reference genome sequence to integrate multiple genome-scale data types, including dRNA-Seq, RNA-Seq and ribosome profiling. Data integration results in the precise determination of 2659 transcription start sites which reveal transcriptional and translational regulatory elements, including −10 and −35 promoter components specific to sigma (σ) factors, and 5′-untranslated region as a determinant for translation efficiency regulation. Particularly, sequence analysis of a wide diversity of the −35 components enables us to predict potential σ-factor regulons, along with various spacer lengths between the −10 and −35 elements. At last, the primary transcriptome landscape of the β-lactam biosynthetic pathway is analyzed, suggesting temporal changes in metabolism for the synthesis of secondary metabolites driven by transcriptional regulation. This comprehensive genetic information provides a versatile genetic resource for rational engineering of secondary metabolite BGCs in Streptomyces.
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