Proteomics

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Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production


ABSTRACT: Heterologous expression of polyketide synthase (PKS) genes in Escherichia coli has enabled the production of various valuable natural and synthetic products. However, the limited availability of malonyl-CoA (M-CoA) in E. coli remains a significant impediment to high-titer polyketide production. In this study, we address this limitation by disrupting the native M-CoA biosynthetic pathway and introducing an orthogonal pathway comprising a malonate transporter and M-CoA ligase, enabling efficient M-CoA biosynthesis under malonate supplementation. This approach significantly increases M-CoA levels, enhancing fatty acid and polyketide titers while reducing the promiscuous activity of PKSs toward undesired acyl-CoA substrates. Subsequent adaptive laboratory evolution of these strains provides insights into M-CoA regulation and identifies mutations that further boost M-CoA and polyketide production. This strategy improves E. coli as a host for polyketide biosynthesis and advances understanding of M-CoA metabolism in microbial systems.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Escherichia Coli

SUBMITTER: Christopher Petzold  

LAB HEAD: Christopher J.

PROVIDER: PXD060741 | Pride | 2025-02-13

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
E1S2_JBx_265998-R1.raw Raw
E1S2_JBx_265998-R2.raw Raw
E1S2_JBx_265998-R3.raw Raw
E1S2_JBx_265998-R4.raw Raw
E2S3_JBx_266007-R1.raw Raw
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