Microbial cell factories · 2025
Engineered biosynthesis and characterization of disaccharide-pimaricin.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zuo Xiaoshan, Qiao Liqin, Dong Yao, Jin Xing, Ren Zhongyuan, Cui Hao
Аннотация
BACKGROUND: Disaccharide polyene macrolides exhibit superior water solubility and significantly reduced hemolytic toxicity compared to their monosaccharide counterparts, making them promising candidates for safer antifungal therapeutics. In this study, we engineered a Streptomyces gilvosporeus (pSET152-nppY) capable of producing disaccharide-pimaricin (DSP) through heterologous expression of the nppY gene, which encodes a glycosyltransferase responsible for the second sugar extension in the biosynthetic pathway.
RESULTS: The novel compound was structurally characterized and designated disaccharide-pimaricin (DSP), featuring an aglycone identical to pimaricin and a unique disaccharide moiety (mycosaminyl-α1-4-N-acetylglucosamine). A purification protocol for DSP was established. Compared to pimaricin, DSP demonstrated a 50% reduction in antifungal activity, a 12.6-fold decrease in hemolytic toxicity, and a remarkable 107.6-fold increase in water solubility. Growth analysis revealed a delayed growth cycle in the mutant strain, suggesting that nppY expression may impose additional metabolic burden. Optimization of the fermentation medium using a statistical design identified an optimal formulation, with a maximum DSP titer of 138.168 mg/L.
CONCLUSIONS: This study underscores the potential of disaccharide polyene macrolides as safer antifungal agents and establishes a robust framework for engineering strains to produce these compounds. The findings provide critical insights into balancing biosynthetic efficiency and strain fitness, advancing the development of next-generation polyene antibiotics.
RESULTS: The novel compound was structurally characterized and designated disaccharide-pimaricin (DSP), featuring an aglycone identical to pimaricin and a unique disaccharide moiety (mycosaminyl-α1-4-N-acetylglucosamine). A purification protocol for DSP was established. Compared to pimaricin, DSP demonstrated a 50% reduction in antifungal activity, a 12.6-fold decrease in hemolytic toxicity, and a remarkable 107.6-fold increase in water solubility. Growth analysis revealed a delayed growth cycle in the mutant strain, suggesting that nppY expression may impose additional metabolic burden. Optimization of the fermentation medium using a statistical design identified an optimal formulation, with a maximum DSP titer of 138.168 mg/L.
CONCLUSIONS: This study underscores the potential of disaccharide polyene macrolides as safer antifungal agents and establishes a robust framework for engineering strains to produce these compounds. The findings provide critical insights into balancing biosynthetic efficiency and strain fitness, advancing the development of next-generation polyene antibiotics.