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Correlational networking guides the discovery of unclustered lanthipeptide protease-encoding genes.
Xue, Dan; Older, Ethan A; Zhong, Zheng; Shang, Zhuo; Chen, Nanzhu; Dittenhauser, Nolan; Hou, Lukuan; Cai, Peiyan; Walla, Michael D; Dong, Shi-Hui; Tang, Xiaoyu; Chen, Hexin; Nagarkatti, Prakash; Nagarkatti, Mitzi; Li, Yong-Xin; Li, Jie.
Affiliation
  • Xue D; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.
  • Older EA; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.
  • Zhong Z; Department of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • Shang Z; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.
  • Chen N; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.
  • Dittenhauser N; Department of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • Hou L; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.
  • Cai P; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.
  • Walla MD; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.
  • Dong SH; Department of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • Tang X; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.
  • Chen H; The Mass Spectrometry Center, Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.
  • Nagarkatti P; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China.
  • Nagarkatti M; Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China.
  • Li YX; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA.
  • Li J; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.
Nat Commun ; 13(1): 1647, 2022 03 28.
Article in En | MEDLINE | ID: mdl-35347143
Bacterial natural product biosynthetic genes, canonically clustered, have been increasingly found to rely on hidden enzymes encoded elsewhere in the genome for completion of biosynthesis. The study and application of lanthipeptides are frequently hindered by unclustered protease genes required for final maturation. Here, we establish a global correlation network bridging the gap between lanthipeptide precursors and hidden proteases. Applying our analysis to 161,954 bacterial genomes, we establish 5209 correlations between precursors and hidden proteases, with 91 prioritized. We use network predictions and co-expression analysis to reveal a previously missing protease for the maturation of class I lanthipeptide paenilan. We further discover widely distributed bacterial M16B metallopeptidases of previously unclear biological function as a new family of lanthipeptide proteases. We show the involvement of a pair of bifunctional M16B proteases in the production of previously unreported class III lanthipeptides with high substrate specificity. Together, these results demonstrate the strength of our correlational networking approach to the discovery of hidden lanthipeptide proteases and potentially other missing enzymes for natural products biosynthesis.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptide Hydrolases / Genome, Bacterial Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: United States Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptide Hydrolases / Genome, Bacterial Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: United States Country of publication: United kingdom