Genetic make-up and regulation of the L-lysine biosynthesis pathway in Vibrio natriegens
Authors:Elly Straube1, Johannes Radde1, Thi Van Anh Tran1, Negin Keihani Yazdi1, Rubén Crespo Blanco1, Ha Thanh Le2, Cláudio J.R. Frazão1 and Thomas Walther1,*
doi: 10.15698/mic2026.02.867
Volume 13, pp. 44 to 62, published 03/02/2026.
1 Institute of Natural Materials Technology, TU Dresden, 01062 Dresden, Germany. 2 School of Chemistry and Life Science, Hanoi University of Science and Technology, 1 Dai Co Viet, Hanoi, Vietnam.
Keywords:
L-lysine biosynthesis, aspartate-family amino acids, Vibrio natriegens, transcriptome analysis
Corresponding Author(s):
Conflict of interest statement:
None declared.
Please cite this article as:
Elly Straube, Johannes Radde, Thi Van Anh Tran, Negin Keihani Yazdi, Rubén Crespo Blanco, Ha Thanh Le, Cláudio J.R. Frazão, Thomas Walther (2026). Genetic make-up and regulation of the L-lysine biosynthesis pathway in Vibrio natriegens. Microbial Cell 13: 44-62. doi: 10.15698/mic2026.02.867
© 2026 Straube et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Vibrio natriegens, the fastest growing non-pathogenic microorganism known to date, has emerged as a highly promising chassis strain for synthetic biology and biotechnology applications. This study analysed the make-up and regulation of the biosynthetic pathway for L-lysine and related L-aspartate family amino acids (AFAAs) in V. natriegens DSM759 to provide a comprehensive basis for future metabolic engineering endeavours aiming at developing this strain into an amino acid overproducer. The compilation of automatically annotated genome sequencing data revealed the presence of gene duplicates encoding putative isozymes for multiple enzymatic reactions within these pathways. The physiological role of these isozymes was analysed via growth phenotyping of corresponding gene deletion mutants as well as enzymatic assays. We verified the presence of a previously unknown mono-functional aspartate kinase isozyme, here termed Vn.LysC2, which was shown to be insensitive to allosteric inhibition by any AFAA. In addition, functional duplicates of L-aspartate semialdehyde dehydrogenase and dihydrodipicolinate synthase enzymes were identified. RNA sequencing experiments were used to elucidate the transcriptional regulation mediated by AFAAs on both their corresponding biosynthetic pathways as well as on the global metabolism. The presence of L-lysine, L-threonine, L-isoleucine and L-methionine resulted in the transcriptional repression of their respective biosynthetic pathways. A global analysis of the transcriptional response revealed that the transcriptional response to L-lysine and L-isoleucine was characterised by a high degree of specificity (four and seven differentially expressed genes, respectively), while L-methionine and L-threonine supplementation affected the expression of a larger number of genes (37 and 60 differentially expressed genes).