Scholarlink

<p><i>Cladosporium variabile</i> (<i>C. variabile</i>) is a potential taxane-producing endophytic fungus; however, its intrinsic production of anticancer taxane metabolites remains low. This investigation systematically bridges this gap by integrating biotechnological strategies e.g., optimization (including acidity, carbon and nitrogen source), elicitation, computational modeling, and molecular dynamics (MD). It was found that pH 6.0 led to the taxane fermentation of 7.4&#xa0;µg gFW<sup>− 1</sup>. Malt 5.0% (w/v) at pH 6.0 boosted the growth and taxane yield by 1.3 fold. At pH 6.0, malt 5.0% (w/v) and ammonium sulfate 5.0 mM significantly enhanced the taxane production to 24.62&#xa0;µg gFW<sup>− 1</sup>. Pectin elicitation further amplified this yield by 31-fold, achieving 233&#xa0;µg gFW<sup>− 1</sup> at day 14. Mathematical modeling indicated that the optimal pH range for the growth and taxane fermentation was between 5.4 and 6.3. Moreover, modeling the concentrations of malt and ammonium sulfate predicted improvements in both growth and taxane yield, offering valuable approaches for medium optimization. MD simulations of taxadiene synthase (TXS) revealed key molecular interactions between TXS and pectin, particularly involving residues Lys873, Val415, Arg421, and Pro661. Root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analysis determined that pectin binding significantly stabilized TXS, decreasing the average RMSD from 4.7 Å to 3.1 Å and reducing backbone fluctuations. These findings highlight the potential of optimized fermentation and sustainable elicitation strategies to address current limitations in taxane production. Furthermore, molecular dynamics simulations provided insights into key binding interactions, offering a foundation for improved biotechnological applications and sustainable platforms for taxane biosynthesis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Biotechnological insights into taxane biosynthesis by Cladosporium variabile: fermentation optimization, elicitation, modeling, and molecular dynamics

  • 期刊论文

  • 发表日期：

    2026年3月5日

查看全文
  • Hamzeh Rezazadeh,
  • Faezeh Ghanati,
  • Mercedes Bonfill,
  • Narjes Mohammadi Ballakuti

摘要

Cladosporium variabile (C. variabile) is a potential taxane-producing endophytic fungus; however, its intrinsic production of anticancer taxane metabolites remains low. This investigation systematically bridges this gap by integrating biotechnological strategies e.g., optimization (including acidity, carbon and nitrogen source), elicitation, computational modeling, and molecular dynamics (MD). It was found that pH 6.0 led to the taxane fermentation of 7.4 µg gFW− 1. Malt 5.0% (w/v) at pH 6.0 boosted the growth and taxane yield by 1.3 fold. At pH 6.0, malt 5.0% (w/v) and ammonium sulfate 5.0 mM significantly enhanced the taxane production to 24.62 µg gFW− 1. Pectin elicitation further amplified this yield by 31-fold, achieving 233 µg gFW− 1 at day 14. Mathematical modeling indicated that the optimal pH range for the growth and taxane fermentation was between 5.4 and 6.3. Moreover, modeling the concentrations of malt and ammonium sulfate predicted improvements in both growth and taxane yield, offering valuable approaches for medium optimization. MD simulations of taxadiene synthase (TXS) revealed key molecular interactions between TXS and pectin, particularly involving residues Lys873, Val415, Arg421, and Pro661. Root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analysis determined that pectin binding significantly stabilized TXS, decreasing the average RMSD from 4.7 Å to 3.1 Å and reducing backbone fluctuations. These findings highlight the potential of optimized fermentation and sustainable elicitation strategies to address current limitations in taxane production. Furthermore, molecular dynamics simulations provided insights into key binding interactions, offering a foundation for improved biotechnological applications and sustainable platforms for taxane biosynthesis.