RRC ID 54482
著者 Takayama S, Ozaki A, Konishi R, Otomo C, Kishida M, Hirata Y, Matsumoto T, Tanaka T, Kondo A.
タイトル Enhancing 3-hydroxypropionic acid production in combination with sugar supply engineering by cell surface-display and metabolic engineering of Schizosaccharomyces pombe.
ジャーナル Microb Cell Fact
Abstract BACKGROUND:Economical production of value-added chemicals from renewable biomass is a promising path to sustainability. 3-Hydroxypropionic acid (3-HP) is an important chemical for building a bio-sustainable society. Establishment of 3-HP production from renewable resources such as glucose would provide a bio-sustainable alternative to the production of acrylic acid from fossil resources.
RESULTS:Here, we describe metabolic engineering of the fission yeast Schizosaccharomyces pombe to enhance 3-HP production from glucose and cellobiose via the malonyl-CoA pathway. The mcr gene, encoding the malonyl-CoA reductase of Chloroflexus aurantiacus, was dissected into two functionally distinct fragments, and the activities of the encoded protein were balanced. To increase the cellular supply of malonyl-CoA and acetyl-CoA, we introduced genes encoding endogenous aldehyde dehydrogenase, acetyl-CoA synthase from Salmonella enterica, and endogenous pantothenate kinase. The resulting strain produced 3-HP at 1.0 g/L from a culture starting at a glucose concentration of 50 g/L. We also engineered the sugar supply by displaying beta-glucosidase (BGL) on the yeast cell surface. When grown on 50 g/L cellobiose, the beta-glucosidase-displaying strain consumed cellobiose efficiently and produced 3-HP at 3.5 g/L. Under fed-batch conditions starting from cellobiose, this strain produced 3-HP at up to 11.4 g/L, corresponding to a yield of 11.2% (g-3-HP/g-glucose; given that 1 g cellobiose corresponds to 1.1 g glucose upon digestion).
CONCLUSIONS:In this study, we constructed a series of S. pombe strains that produced 3-HP via the malonyl-CoA pathway. Our study also demonstrated that BGL display using cellobiose and/or cello-oligosaccharides as a carbon source has the potential to improve the titer and yield of malonyl-CoA- and acetyl-CoA-derived compounds.
巻・号 17(1)
ページ 176
公開日 2018-11-13
DOI 10.1186/s12934-018-1025-5
PII 10.1186/s12934-018-1025-5
PMID 30424766
PMC PMC6234659
MeSH Acetyl Coenzyme A / metabolism Batch Cell Culture Techniques Carbon / pharmacology Lactic Acid / analogs & derivatives* Lactic Acid / biosynthesis Malonyl Coenzyme A / metabolism Metabolic Engineering / methods* Metabolic Networks and Pathways / drug effects Oxidoreductases / metabolism Schizosaccharomyces / cytology* Schizosaccharomyces / drug effects Schizosaccharomyces / metabolism* Sugars / metabolism*
IF 4.187
引用数 4
リソース情報
遺伝子材料 pDUAL-FFH1 (RDB06185) pDUAL-FFH31 (RDB06536) pDUAL-FFH61 (RDB06538)