Correlational networking guides the discovery of unclustered lanthipeptide protease-encoding genes

Dan Xue, Ethan A. Older, Zheng Zhong, Zhuo Shang, Nanzhu Chen, Nolan Dittenhauser, Lukuan Hou, Peiyan Cai, Michael D. Walla, Shi-Hui Dong, Xiaoyu Tang, Hexin Chen, Prakash Nagarkatti, Mitzi Nagarkatti, Yong-Xin Li () and Jie Li ()
Additional contact information
Dan Xue: University of South Carolina
Ethan A. Older: University of South Carolina
Zheng Zhong: The University of Hong Kong
Zhuo Shang: University of South Carolina
Nanzhu Chen: The University of Hong Kong
Nolan Dittenhauser: University of South Carolina
Lukuan Hou: University of South Carolina
Peiyan Cai: The University of Hong Kong
Michael D. Walla: University of South Carolina
Shi-Hui Dong: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University
Xiaoyu Tang: Institute of Chemical Biology, Shenzhen Bay Laboratory
Hexin Chen: University of South Carolina
Prakash Nagarkatti: University of South Carolina
Mitzi Nagarkatti: University of South Carolina
Yong-Xin Li: The University of Hong Kong
Jie Li: University of South Carolina

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29325-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29325-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29325-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().