Phenotype-genotype mapping reveals the betaine-triggered L-arginine overproduction mechanism in Escherichia coli

The production phenotype improvement of industrial microbes is extremely needed and challenging. Environ-mental factors optimization provides insightful ideas to trigger the superior production phenotype by activating potential genetic determiners. Here, phenotype-genotype mapping was used to dissect the betaine-triggered L-arginine overproduction mechanism and mine beneficial genes for further improving production phenotype. The comparative transcriptomic analysis revealed a novel role for betaine in modulating global gene transcription. Guided by this finding, 4 novel genes (cynX, cynT, pyrB, and rhaB) for L-arginine biosynthesis were identified via reverse engineering. Moreover, the rhaB deletion was demonstrated as a common metabolic engineering strategy to improve ATP pool in E. coli. By combinatorial genes manipulation, the L-arginine titer and yield increased by 17.9% and 28.9% in a 5-L bioreactor without betaine addition. This study revealed the molecular mechanism of gene transcription regulation by betaine and developed a superior L-arginine overproducer that does not require betaine.

Automated summary

The improvement of industrial microbes' production phenotype is necessary and challenging. Optimizing environmental factors helps to activate potential genetic determiners and enhance production. This study dissected the mechanism of L-arginine overproduction triggered by betaine and identified beneficial genes for further improvement. It also revealed the role of betaine in modulating gene transcription and developed a superior L-arginine overproducer that does not require betaine.