Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi

ABSTRACT The oleaginous yeast Lipomyces starkeyi is recognized for its remarkable lipid accumulation under nitrogen‐limited conditions. However, precise control of microbial lipid production in L. starkeyi remains challenging due to the complexity of nutrient media. We developed a two‐stage fed‐batc...

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Main Authors: Chih‐Chan Wu, Kenji Okano, Pijar Religia, Yuki Soma, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Kohsuke Honda
Format: Article
Language:English
Published: Wiley-VCH 2025-01-01
Series:Engineering in Life Sciences
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Online Access:https://doi.org/10.1002/elsc.70003
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author Chih‐Chan Wu
Kenji Okano
Pijar Religia
Yuki Soma
Masatomo Takahashi
Yoshihiro Izumi
Takeshi Bamba
Kohsuke Honda
author_facet Chih‐Chan Wu
Kenji Okano
Pijar Religia
Yuki Soma
Masatomo Takahashi
Yoshihiro Izumi
Takeshi Bamba
Kohsuke Honda
author_sort Chih‐Chan Wu
collection DOAJ
description ABSTRACT The oleaginous yeast Lipomyces starkeyi is recognized for its remarkable lipid accumulation under nitrogen‐limited conditions. However, precise control of microbial lipid production in L. starkeyi remains challenging due to the complexity of nutrient media. We developed a two‐stage fed‐batch fermentation process using a well‐defined synthetic medium in a 5‐L bioreactor. In the first stage, the specific growth rate was maintained at a designated level by maximizing the cell density through optimizing the feeding rate, molar carbon‐to‐nitrogen (C/N) ratio, and phosphate concentration in feeding media, achieving a high cell density of 213 ± 10 × 107 cells mL−1. In the second stage, we optimized the molar C/N ratio in the feeding medium for lipid production and achieved high biomass (130 ± 5 g L−1), lipid titer (88 ± 6 g L−1), and lipid content (67% ± 2% of dry cellular weight). Our approach yielded a high lipid titer, comparable to the highest reported value of 68 g L−1 achieved in a nutrient medium, by optimizing cultivation conditions with a synthetic medium in L. starkeyi. This highlights the importance of well‐established yet powerful bioprocess approaches for the precise control of microbial cultivation.
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id doaj-art-4e986b5ce4f84914b03eee11871cb39c
institution Kabale University
issn 1618-0240
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language English
publishDate 2025-01-01
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record_format Article
series Engineering in Life Sciences
spelling doaj-art-4e986b5ce4f84914b03eee11871cb39c2025-01-30T06:40:31ZengWiley-VCHEngineering in Life Sciences1618-02401618-28632025-01-01251n/an/a10.1002/elsc.70003Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyiChih‐Chan Wu0Kenji Okano1Pijar Religia2Yuki Soma3Masatomo Takahashi4Yoshihiro Izumi5Takeshi Bamba6Kohsuke Honda7International Center for Biotechnology Osaka University Suita Osaka JapanInternational Center for Biotechnology Osaka University Suita Osaka JapanInternational Center for Biotechnology Osaka University Suita Osaka JapanSynthetic Bioengineering Research Group Bioproduction Research Institute National Institute of Advanced Industrial Science and Technology Tsukuba Ibaraki JapanDivision of Metabolomics/Mass Spectrometry Center Medical Research Center for High Depth Omics Medical Institute of Bioregulation Kyushu University Fukuoka JapanDivision of Metabolomics/Mass Spectrometry Center Medical Research Center for High Depth Omics Medical Institute of Bioregulation Kyushu University Fukuoka JapanDivision of Metabolomics/Mass Spectrometry Center Medical Research Center for High Depth Omics Medical Institute of Bioregulation Kyushu University Fukuoka JapanInternational Center for Biotechnology Osaka University Suita Osaka JapanABSTRACT The oleaginous yeast Lipomyces starkeyi is recognized for its remarkable lipid accumulation under nitrogen‐limited conditions. However, precise control of microbial lipid production in L. starkeyi remains challenging due to the complexity of nutrient media. We developed a two‐stage fed‐batch fermentation process using a well‐defined synthetic medium in a 5‐L bioreactor. In the first stage, the specific growth rate was maintained at a designated level by maximizing the cell density through optimizing the feeding rate, molar carbon‐to‐nitrogen (C/N) ratio, and phosphate concentration in feeding media, achieving a high cell density of 213 ± 10 × 107 cells mL−1. In the second stage, we optimized the molar C/N ratio in the feeding medium for lipid production and achieved high biomass (130 ± 5 g L−1), lipid titer (88 ± 6 g L−1), and lipid content (67% ± 2% of dry cellular weight). Our approach yielded a high lipid titer, comparable to the highest reported value of 68 g L−1 achieved in a nutrient medium, by optimizing cultivation conditions with a synthetic medium in L. starkeyi. This highlights the importance of well‐established yet powerful bioprocess approaches for the precise control of microbial cultivation.https://doi.org/10.1002/elsc.70003fermentationhigh cell densityLipomyces starkeyimicrobial lipidoleaginous yeastsynthetic medium
spellingShingle Chih‐Chan Wu
Kenji Okano
Pijar Religia
Yuki Soma
Masatomo Takahashi
Yoshihiro Izumi
Takeshi Bamba
Kohsuke Honda
Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi
Engineering in Life Sciences
fermentation
high cell density
Lipomyces starkeyi
microbial lipid
oleaginous yeast
synthetic medium
title Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi
title_full Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi
title_fullStr Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi
title_full_unstemmed Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi
title_short Combination of Two‐Stage Continuous Feeding and Optimized Synthetic Medium Increases Lipid Production in Lipomyces starkeyi
title_sort combination of two stage continuous feeding and optimized synthetic medium increases lipid production in lipomyces starkeyi
topic fermentation
high cell density
Lipomyces starkeyi
microbial lipid
oleaginous yeast
synthetic medium
url https://doi.org/10.1002/elsc.70003
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