4.7 Article

Production of fengycin from D-xylose through the expression and metabolic regulation of the Dahms pathway

Journal

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume 106, Issue 7, Pages 2557-2567

Publisher

SPRINGER
DOI: 10.1007/s00253-022-11871-9

Keywords

Fengycin; D-Xylose; Dahms pathway; Bacillus subtilis 168; Metabolic engineering

Funding

  1. National Key Research and Development Program of China [2018YFA0902200]

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In this study, the genes of the Dahms xylose-utilization pathway were integrated into Bacillus subtilis and a metabolic control module was designed, resulting in an increased yield of fengycin. Metabonomic analysis revealed the underlying factors for the increase of fengycin titer.
D-Xylose is a key component of lignocellulosic biomass and the second-most abundant carbohydrate on the planet. As one of the most powerful cyclo-lipopeptide antibiotics, fengycin displays strong wide-spectrum antifungal and antiviral, as well as potential anti-cancer activity. Pyruvate is a key metabolite linking the biosynthesis of fatty acids and amino acids, the precursors for fengycin. In this study, the genes encoding the Dahms xylose-utilization pathway were integrated into the amyE site of Bacillus subtilis 168, and based on the metabolic characteristics of the Dahms pathway, the acetate kinase (ackA) and lactate dehydrogenase (ldh) genes were knocked out. Then, the metabolic control module II was designed to convert glycolaldehyde, another intermediate of the Dahms pathway, in addition to pathways for the conversion of acetaldehyde into malic acid and oxaloacetic acid, resulting in strain BSU03. In the presence of module II, the content of acetic and lactic acid decreased significantly, and the xylose uptake efficiency increased. At the same time, the yield of fengycin increased by 87% compared to the original strain. Additionally, the underlying factors for the increase of fengycin titer were revealed through metabonomic analysis. This study therefore demonstrates that this regulation approach can not only optimize the intracellular fluxes for the Dahms pathway, but is also conducive to the synthesis of secondary metabolites similar to fengycin.

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