Jing-Ke Weng received his B.S. (2003) in Biotechnology from Zhejiang University, Hangzhou, China. He received his Ph.D. (2009) in Biochemistry from Purdue University, and was a pioneer postdoctoral fellow at the Salk Institute for Biological Studies and Howard Hughs Medical Institute between 2009 and 2013. Currently he is a member of the Whitehead Institue for Biomedical Research, and a Thomas D. and Virginia W. Cabot Assistant Professor of Biology at Massachusetts Institute of Technology. Dr. Weng's research focuses on understanding the origin and evolution of plant specialized metabolism at enzyme, pathway, and systems levels, as well as how plants exploit discrete small molecules to interact with their surrounding biotic and abiotic environments. Through synthetic biology and metabolic engineering approaches, he develops new platforms for producing high-value natural products in a sustainable manner. In addition, he utilizes plant as a unique model system to study human diseases, including metabolic syndromes and protein-misfolding diseases. Dr. Weng has won numerous awards in his career, including Beckman Young Investigator (2016), Alfred P. Sloan Research Fellow (2016), Searle Scholar (2015), Pew Scholar in the Biomedical Sciences (2014), American Society of Plant Biologists Early Career Award (2014), and Tansley Medal for Excellence in Plant Science (2013).
Gene-guided discovery and engineering of branched cyclic peptides in plants
Jing-Ke Weng 1,2
1 Whitehead Institute for Biomedical Research
2 Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142-1479
The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer a unique class of branched cyclic plant peptides, the lyciumins. Initially isolated from the Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate and a macrocyclic bond between a tryptophan-indole nitrogen and a glycine α-carbon. We report the first identification of a lyciumin precursor gene from L. barbarum, which encodes a BURP domain and repetitive lyciumin precursor peptide motifs. Genome and transcriptome mining enabled by this initial finding revealed a rich repertoire of previously unidentified lyciumin genotypes and chemotypes widespread in terrestrial plants. Our results suggest parallel evolution of branched cyclic ribosomal peptide biosynthesis in lycophytes and angiosperms, likely coupled to abiotic stress responses via BURP domain precursor peptides. We establish the biosynthetic framework of lyciumins, and demonstrate the feasibility of producing diverse natural and unnatural lyciumins in transgenic tobacco. This study illustrates a new approach to unlock plant peptide chemistry and biochemistry with broad pharmaceutical and agrochemical applications.