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Enhancing 3-hydroxypropionic acid production in combination with sugar supply engineering by cell surface-display and metabolic engineering of Schizosaccharomyces pombe

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논문

Enhancing 3-hydroxypropionic acid production in combination with sugar supply engineering by cell surface-display and metabolic engineering of Schizosaccharomyces pombe

학술지

Microbial cell factories

저자명

Takayama, Seiya; Ozaki, Aiko; Konishi, Rie; Otomo, Chisako; Kishida, Mayumi; Hirata, Yuuki; Matsumoto, Takuya; Tanaka, Tsutomu; Kondo, Akihiko

초록

<P><B>Background</B></P><P>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.</P><P><B>Results</B></P><P>Here, we describe metabolic engineering of the fission yeast S<I>chizosaccharomyces pombe</I> to enhance 3-HP production from glucose and cellobiose via the malonyl-CoA pathway. The <I>mcr</I> gene, encoding the malonyl-CoA reductase of <I>Chloroflexus aurantiacus</I>, 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 <I>Salmonella enterica</I>, and endogenous pantothenate kinase. The resulting strain produced 3-HP at 1.0&nbsp;g/L from a culture starting at a glucose concentration of 50&nbsp;g/L. We also engineered the sugar supply by displaying beta-glucosidase (BGL) on the yeast cell surface. When grown on 50&nbsp;g/L cellobiose, the beta-glucosidase-displaying strain consumed cellobiose efficiently and produced 3-HP at 3.5&nbsp;g/L. Under fed-batch conditions starting from cellobiose, this strain produced 3-HP at up to 11.4&nbsp;g/L, corresponding to a yield of 11.2% (g-3-HP/g-glucose; given that 1&nbsp;g cellobiose corresponds to 1.1&nbsp;g glucose upon digestion).</P><P><B>Conclusions</B></P><P>In this study, we constructed a series of <I>S. pombe</I> 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.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s12934-018-1025-5) contains supplementary material, which is available to authorized users.</P>

발행연도

2018

발행기관

BioMed Central

라이선스

cc-by

ISSN

1475-2859

17

페이지

pp.176

주제어

Schizosaccharomyces pombe; 3-Hydroxypropionic acid; CRISPR&#x2013; Cas9 system; Cell surface display; Malonyl-CoA;

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논문; 2018-11-13

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