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Background <p>Microbial metabolic engineering increasingly depends on identifying robust non-conventional yeast chassis with favorable metabolic traits. Although <i>Saccharomyces cerevisiae</i> remains the main model for isoprenoid engineering, alternative yeasts may provide superior native precursor availability. Here, we report the first comparative metabolomic characterization of Saccharomycopsis fibuligera, focusing on the mevalonate and terpenoid backbone biosynthesis pathways.</p> Results <p>LC-MS profiling revealed elevated levels of acetyl-CoA, HMG-CoA, and MVA in <i>S. fibuligera</i>, suggesting strong native flux through the MVA pathway. The universal isoprenoid precursors IPP and DMAPP accumulated at substantially higher levels than in <i>S. cerevisiae</i>, together with enrichment of FPP and ergosterol abundance, indicating efficient channeling toward sterol biosynthesis. Conversely, upper glycolysis metabolites were reduced, while TCA cycle intermediates were enriched, supporting the proposed Crabtree-negative phenotype of <i>S. fibuligera</i>. Amino acid profiling also indicated enhanced nitrogen storage capacity.</p> Conclusions <p>These results position <i>S. fibuligera</i> as a metabolically favorable platform with high intrinsic MVA pathway activity and precursor availability for terpenoid production, highlighting its strong potential as an emerging microbial chassis for next‑generation terpenoid bioproduction.</p>

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Snapshot at Saccharomycopsis fibuligera metabolism for industrial terpenoid production and bioengineering

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Alejandro Lopez-Barbera,
  • Helena Torrell,
  • Nerea Abasolo,
  • Núria Canela,
  • Salvador Fernández-Arroyo

摘要

Background

Microbial metabolic engineering increasingly depends on identifying robust non-conventional yeast chassis with favorable metabolic traits. Although Saccharomyces cerevisiae remains the main model for isoprenoid engineering, alternative yeasts may provide superior native precursor availability. Here, we report the first comparative metabolomic characterization of Saccharomycopsis fibuligera, focusing on the mevalonate and terpenoid backbone biosynthesis pathways.

Results

LC-MS profiling revealed elevated levels of acetyl-CoA, HMG-CoA, and MVA in S. fibuligera, suggesting strong native flux through the MVA pathway. The universal isoprenoid precursors IPP and DMAPP accumulated at substantially higher levels than in S. cerevisiae, together with enrichment of FPP and ergosterol abundance, indicating efficient channeling toward sterol biosynthesis. Conversely, upper glycolysis metabolites were reduced, while TCA cycle intermediates were enriched, supporting the proposed Crabtree-negative phenotype of S. fibuligera. Amino acid profiling also indicated enhanced nitrogen storage capacity.

Conclusions

These results position S. fibuligera as a metabolically favorable platform with high intrinsic MVA pathway activity and precursor availability for terpenoid production, highlighting its strong potential as an emerging microbial chassis for next‑generation terpenoid bioproduction.