GENETIC ENGINEERING OF Sorangium cellulosum: A PLATFORM FOR DECODING MYXOBACTERIAL SECONDARY METABOLISM
Abstract
Sorangium cellulosum is a cellulolytic myxobacterium renowned for producing a vast array of complex natural products with diverse chemical scaffolds and biological activities, including the anticancer drug epothilones. Despite its remarkable biosynthetic potential, progress in understanding and harnessing these metabolites has been hampered by the lack of effective genetic manipulation tools. To address this challenge, we have developed a versatile genetic engineering method applicable across multiple Sorangium cellulosum strains, effectively overcoming their genetic intractability. This facilitated delineation of the biosynthetic pathways to several biologically important natural products including ambruticin, jerangolid and carolacton. Our findings reveal a series of biosynthetic steps characterised by remarkable enzymology, offering significant insights into the molecular machinery governing myxobacterial natural product biosynthesis. Our work establishes a robust platform for further pathway engineering of Sorangium strains, opening new avenues for expanding the chemical and biological diversity accessible from myxobacteria.
References
- Xiaotong Zhong, Shan Liu, Bingda Ma, Kaining Gao, Dayong Jiang, Yingshuo Hou, Huliang Chen, Jiaqi Lv, James I. Bowen, Matthew P. Crump, Christine L. Willis, Luoyi Wang. (2025). Genetic engineering of Sorangium cellulosum reveals hidden enzymology in myxobacterial natural product biosynthesis.Nature Communications.[Crossref]
- James I. Bowen, Xiaotong Zhong, Kaining Gao, Benjamin Reed, Matthew P. Crump, Luoyi Wang, Christine L. Willis. (2024). Combining total synthesis and genetic engineering to probe dihydropyran formation in ambruticin biosynthesis.Chemical Science.[Crossref]
Publication Details
This article is licensed under a Creative Commons Attribution 4.0 International License.