Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha
Abstract Background One carbon (C1) molecules such as methanol have the potential to become sustainable feedstocks for biotechnological processes, as they can be derived from CO2 and green hydrogen, without the need for arable land. Therefore, we investigated the suitability of the methylotrophic ye...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Microbial Cell Factories |
| Online Access: | https://doi.org/10.1186/s12934-023-02283-z |
| _version_ | 1797362741076295680 |
|---|---|
| author | Katrin Wefelmeier Simone Schmitz Benjamin Jonas Kösters Ulf Winfried Liebal Lars Mathias Blank |
| author_facet | Katrin Wefelmeier Simone Schmitz Benjamin Jonas Kösters Ulf Winfried Liebal Lars Mathias Blank |
| author_sort | Katrin Wefelmeier |
| collection | DOAJ |
| description | Abstract Background One carbon (C1) molecules such as methanol have the potential to become sustainable feedstocks for biotechnological processes, as they can be derived from CO2 and green hydrogen, without the need for arable land. Therefore, we investigated the suitability of the methylotrophic yeast Ogataea polymorpha as a potential production organism for platform chemicals derived from methanol. We selected acetone, malate, and isoprene as industrially relevant products to demonstrate the production of compounds with 3, 4, or 5 carbon atoms, respectively. Results We successfully engineered O. polymorpha for the production of all three molecules and demonstrated their production using methanol as carbon source. We showed that the metabolism of O. polymorpha is well suited to produce malate as a product and demonstrated that the introduction of an efficient malate transporter is essential for malate production from methanol. Through optimization of the cultivation conditions in shake flasks, which included pH regulation and constant substrate feeding, we were able to achieve a maximum titer of 13 g/L malate with a production rate of 3.3 g/L/d using methanol as carbon source. We further demonstrated the production of acetone and isoprene as additional heterologous products in O. polymorpha, with maximum titers of 13.6 mg/L and 4.4 mg/L, respectively. Conclusion These findings highlight how O. polymorpha has the potential to be applied as a versatile cell factory and contribute to the limited knowledge on how methylotrophic yeasts can be used for the production of low molecular weight biochemicals from methanol. Thus, this study can serve as a point of reference for future metabolic engineering in O. polymorpha and process optimization efforts to boost the production of platform chemicals from renewable C1 carbon sources. |
| first_indexed | 2024-03-08T16:11:46Z |
| format | Article |
| id | doaj.art-ccf4fba40e1c4baa89ec1f29a3556702 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-03-08T16:11:46Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-ccf4fba40e1c4baa89ec1f29a35567022024-01-07T12:55:35ZengBMCMicrobial Cell Factories1475-28592024-01-0123111510.1186/s12934-023-02283-zMethanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorphaKatrin Wefelmeier0Simone Schmitz1Benjamin Jonas Kösters2Ulf Winfried Liebal3Lars Mathias Blank4iAMB - Institute of Applied Microbiology, ABBt – Aachen Biology and Biotechnology, RWTH Aachen UniversityiAMB - Institute of Applied Microbiology, ABBt – Aachen Biology and Biotechnology, RWTH Aachen UniversityiAMB - Institute of Applied Microbiology, ABBt – Aachen Biology and Biotechnology, RWTH Aachen UniversityiAMB - Institute of Applied Microbiology, ABBt – Aachen Biology and Biotechnology, RWTH Aachen UniversityiAMB - Institute of Applied Microbiology, ABBt – Aachen Biology and Biotechnology, RWTH Aachen UniversityAbstract Background One carbon (C1) molecules such as methanol have the potential to become sustainable feedstocks for biotechnological processes, as they can be derived from CO2 and green hydrogen, without the need for arable land. Therefore, we investigated the suitability of the methylotrophic yeast Ogataea polymorpha as a potential production organism for platform chemicals derived from methanol. We selected acetone, malate, and isoprene as industrially relevant products to demonstrate the production of compounds with 3, 4, or 5 carbon atoms, respectively. Results We successfully engineered O. polymorpha for the production of all three molecules and demonstrated their production using methanol as carbon source. We showed that the metabolism of O. polymorpha is well suited to produce malate as a product and demonstrated that the introduction of an efficient malate transporter is essential for malate production from methanol. Through optimization of the cultivation conditions in shake flasks, which included pH regulation and constant substrate feeding, we were able to achieve a maximum titer of 13 g/L malate with a production rate of 3.3 g/L/d using methanol as carbon source. We further demonstrated the production of acetone and isoprene as additional heterologous products in O. polymorpha, with maximum titers of 13.6 mg/L and 4.4 mg/L, respectively. Conclusion These findings highlight how O. polymorpha has the potential to be applied as a versatile cell factory and contribute to the limited knowledge on how methylotrophic yeasts can be used for the production of low molecular weight biochemicals from methanol. Thus, this study can serve as a point of reference for future metabolic engineering in O. polymorpha and process optimization efforts to boost the production of platform chemicals from renewable C1 carbon sources.https://doi.org/10.1186/s12934-023-02283-z |
| spellingShingle | Katrin Wefelmeier Simone Schmitz Benjamin Jonas Kösters Ulf Winfried Liebal Lars Mathias Blank Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha Microbial Cell Factories |
| title | Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha |
| title_full | Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha |
| title_fullStr | Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha |
| title_full_unstemmed | Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha |
| title_short | Methanol bioconversion into C3, C4, and C5 platform chemicals by the yeast Ogataea polymorpha |
| title_sort | methanol bioconversion into c3 c4 and c5 platform chemicals by the yeast ogataea polymorpha |
| url | https://doi.org/10.1186/s12934-023-02283-z |
| work_keys_str_mv | AT katrinwefelmeier methanolbioconversionintoc3c4andc5platformchemicalsbytheyeastogataeapolymorpha AT simoneschmitz methanolbioconversionintoc3c4andc5platformchemicalsbytheyeastogataeapolymorpha AT benjaminjonaskosters methanolbioconversionintoc3c4andc5platformchemicalsbytheyeastogataeapolymorpha AT ulfwinfriedliebal methanolbioconversionintoc3c4andc5platformchemicalsbytheyeastogataeapolymorpha AT larsmathiasblank methanolbioconversionintoc3c4andc5platformchemicalsbytheyeastogataeapolymorpha |