دورية أكاديمية
A Pseudomonas taiwanensis malonyl-CoA platform strain for polyketide synthesis.
| العنوان: | A Pseudomonas taiwanensis malonyl-CoA platform strain for polyketide synthesis. |
|---|---|
| المؤلفون: | Schwanemann T; Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany., Otto M; Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany., Wynands B; Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany., Marienhagen J; Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany; Institute of Biotechnology, RWTH Aachen University, Worringer Weg 3, D-52074, Aachen, Germany., Wierckx N; Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany. Electronic address: n.wierckx@fz-juelich.de. |
| المصدر: | Metabolic engineering [Metab Eng] 2023 May; Vol. 77, pp. 219-230. Date of Electronic Publication: 2023 Apr 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: Belgium NLM ID: 9815657 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-7184 (Electronic) Linking ISSN: 10967176 NLM ISO Abbreviation: Metab Eng Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Brugge, Belgium ; Orlando, FL : Academic Press, c1999- |
| مواضيع طبية MeSH: | Malonyl Coenzyme A*/metabolism , Polyketides*/metabolism , Pseudomonas*/classification , Pseudomonas*/genetics , Pseudomonas*/metabolism, Fatty Acids/metabolism ; Resveratrol/metabolism ; Secondary Metabolism ; Stilbenes/metabolism ; Coumaric Acids/metabolism ; Phenylalanine/metabolism ; Genome, Bacterial/genetics ; Sequence Deletion ; Acetyl Coenzyme A/metabolism ; Citrate (si)-Synthase/metabolism ; Pyruvic Acid/metabolism ; Phytoalexins/metabolism ; Naphthoquinones/metabolism |
| مستخلص: | Malonyl-CoA is a central precursor for biosynthesis of a wide range of complex secondary metabolites. The development of platform strains with increased malonyl-CoA supply can contribute to the efficient production of secondary metabolites, especially if such strains exhibit high tolerance towards these chemicals. In this study, Pseudomonas taiwanensis VLB120 was engineered for increased malonyl-CoA availability to produce bacterial and plant-derived polyketides. A multi-target metabolic engineering strategy focusing on decreasing the malonyl-CoA drain and increasing malonyl-CoA precursor availability, led to an increased production of various malonyl-CoA-derived products, including pinosylvin, resveratrol and flaviolin. The production of flaviolin, a molecule deriving from five malonyl-CoA molecules, was doubled compared to the parental strain by this malonyl-CoA increasing strategy. Additionally, the engineered platform strain enabled production of up to 84 mg L -1 resveratrol from supplemented p-coumarate. One key finding of this study was that acetyl-CoA carboxylase overexpression majorly contributed to an increased malonyl-CoA availability for polyketide production in dependence on the used strain-background and whether downstream fatty acid synthesis was impaired, reflecting its complexity in metabolism. Hence, malonyl-CoA availability is primarily determined by competition of the production pathway with downstream fatty acid synthesis, while supply reactions are of secondary importance for compounds that derive directly from malonyl-CoA in Pseudomonas. Competing Interests: Declaration of competing interest The authors declare no competing interest. (Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Fatty acid biosynthesis; Flaviolin; Malonyl-CoA; Polyketide; Pseudomonas; Stilbene |
| المشرفين على المادة: | 0 (Fatty Acids) 479-05-0 (flaviolin) 524-14-1 (Malonyl Coenzyme A) 881R434AIB (pinosylvin) 0 (Polyketides) Q369O8926L (Resveratrol) 0 (Stilbenes) 0 (Coumaric Acids) 47E5O17Y3R (Phenylalanine) 72-89-9 (Acetyl Coenzyme A) EC 2.3.3.1 (Citrate (si)-Synthase) 8558G7RUTR (Pyruvic Acid) 0 (Phytoalexins) 0 (Naphthoquinones) |
| SCR Organism: | Pseudomonas taiwanensis |
| تواريخ الأحداث: | Date Created: 20230409 Date Completed: 20240223 Latest Revision: 20240223 |
| رمز التحديث: | 20240223 |
| DOI: | 10.1016/j.ymben.2023.04.001 |
| PMID: | 37031949 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-7184 |
|---|---|
| DOI: | 10.1016/j.ymben.2023.04.001 |