AUTHOR=Mao Jiaqi , Zhang Min , Dai Wenjuan , Fu Chenghao , Wang Zhanzhan , Wang Xiuwen , Yao Qingshou , Kong Linghui , Qin Jiayang 

TITLE=Metabolic perturbation of Streptomyces albulus by introducing NADP-dependent glyceraldehyde 3-phosphate dehydrogenase

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1328321

DOI=10.3389/fmicb.2024.1328321

ISSN=1664-302X

ABSTRACT=<p>The available resources of <italic>Streptomyces</italic> represent a valuable repository of bioactive natural products that warrant exploration. <italic>Streptomyces albulus</italic> is primarily utilized in the industrial synthesis of ε-poly-L-lysine (ε-PL). In this study, the NADP-dependent glyceraldehyde 3-phosphate dehydrogenase (GapN) from <italic>Streptococcus mutans</italic> was heterologously expressed in <italic>S. albulus</italic> CICC11022, leading to elevated intracellular NADPH levels and reduced NADH and ATP concentrations. The resulting perturbation of <italic>S. albulus</italic> metabolism was comprehensively analyzed using transcriptomic and metabolomic methodologies. A decrease in production of ε-PL was observed. The expression of <italic>gapN</italic> significantly impacted on 23 gene clusters responsible for the biosynthesis of secondary metabolites. A comprehensive analysis revealed a total of 21 metabolites exhibiting elevated levels both intracellularly and extracellularly in the <italic>gapN</italic> expressing strain compared to those in the control strain. These findings underscore the potential of <italic>S. albulus</italic> to generate diverse bioactive natural products, thus offering valuable insights for the utilization of known <italic>Streptomyces</italic> resources through genetic manipulation.</p>