What drives the cost of biowaste-to-lipase production? Linking titre, rate and yield to techno-economic performance in batch-to-continuous Pichia pastoris fermentation.

@article{hierro2026what,
  title = {{What drives the cost of biowaste-to-lipase production? Linking titre, rate and yield to techno-economic performance in batch-to-continuous Pichia pastoris fermentation.}},
  author = {Ana G Del Hierro and Violine Raynal and Ruth Ordóñez and Fuensanta Verdú-Navarro and Eoin Casey},
  journal = {Bioresources and bioprocessing},
  year = {2026},
  month = oct,
  doi = {10.1186/s40643-026-01153-x},
  url = {https://europepmc.org/article/MED/42955152},
  note = {CC BY},
}

TY  - JOUR
TI  - What drives the cost of biowaste-to-lipase production? Linking titre, rate and yield to techno-economic performance in batch-to-continuous Pichia pastoris fermentation.
AU  - Ana G Del Hierro
AU  - Violine Raynal
AU  - Ruth Ordóñez
AU  - Fuensanta Verdú-Navarro
AU  - Eoin Casey
PY  - 2026
DA  - 2026/10/29
JO  - Bioresources and bioprocessing
DO  - 10.1186/s40643-026-01153-x
UR  - https://europepmc.org/article/MED/42955152
AB  - Fruit and vegetable (FV) waste represents an underutilized organic stream in Europe, yet its soluble sugar fraction remains poorly exploited as a bioprocess feedstock. Recombinant enzyme production from biowaste is often bottlenecked by heterogeneous substrate composition, low fermentable sugar titres, and uncertain process economics. This study evaluates the techno-economic feasibility of recombinant Candida rugosa lipase type 1 (CRL1) production in Pichia pastoris (Komagataella phaffii) under the constitutive glyceraldehyde-3-phosphate dehydrogenase promoter pGAP across three carbon sources: commercial glucose (Scenario A), mechanically pressed fruit and vegetable juice (Scenario B), and an enzymatically hydrolysed, nanofiltered fruit and vegetablesugar stream (Scenario C). Bench-scale fermentation kinetics were integrated into 24 SuperPro Designer models across four scales (1 to 5000 L nominal vessel capacity; 0.75 to 3750 L working volume) under batch and continuous chemostat (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}D=0.05 h^−1\end{document}) modes. Interpreted through the Titre, Rate, and Yield (TRY) framework, continuous operation on glucose increased volumetric CRL1 productivity 12.6-fold over batch (0.084 vs. 0.06 U L−1 h−1. Conversely, continuous operation on the hydrolysed stream did not improve productivity over batch, indicating potential kinetic inhibition from enzymatic pretreatment products or suboptimal dilution rate. At the 5000 L vessel scale under continuous mode, unit production costs were $1186, $36,049, and 3416 documentclass[12pt]minimal usepackageamsmath usepackagewasysym usepackageamsfonts usepackageamssymb usepackageamsbsy usepackagemathrsfs usepackageupgreek setlengthoddsidemargin−69ptkg^−1for Scenarios A, B, and C, respectively, all exceeding the commodity lipase benchmark (25 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}kg^−1\end{document}). Facility-dependent costs dominated Scenarios A and B (73% and 78% of OPEX), whereas enzyme reagents dominated Scenario C (75%). Sensitivity analysis confirmed that secreted protein titre and downstream recovery efficiency are the primary economic drivers, demonstrating that feedstock acquisition cost is not the binding constraint. Early-stage TEA driven by bench-scale kinetic parameterization provides essential screening prior to pilot-scale investment in biowaste-to-enzyme biorefineries.  Graphical abstract:  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s40643-026-01153-x.
SN  - 2197-4365
ER  -