- Research Article
- 10.1021/acssynbio.5c00354
Development ofa High Anthraquinone-Producing Escherichia coli Strain Using Malonyl-CoA SupplyPathway Engineering
- Sep 16, 2025
- ACS Synthetic Biology
- Takatoshi Suematsu + 5 more +5
Anthraquinones are valuable compounds that are traditionallyusedas natural pigments and have diverse pharmacological activities, includingantimicrobial and anticancer effects. In this study, we aimed to enhancethe production of 1,3,5-trihydroxyanthraquinone (AQ256) using Escherichia coli (E. coli) as a host. AQ256 is biosynthesized from eight malonyl-CoA moleculesvia the type II polyketide synthase pathway. However, previous studieshave reported very low production levels of AQ256 in E. coli (approximately 2.5 mg/L), mainly becauseof limited malonyl-CoA availability. To address this, we introduceda heterologous malonate assimilation pathway and reinforced the endogenousmalonyl-CoA biosynthesis pathway. An E. coli strain harboring AQ256 biosynthetic genes from Photorhabduslaumondii TTO1 produced only 1.3 mg/L AQ256. Uponintroducing the malonate assimilation pathway and cultivating in malonate-supplementedLuria–Bertani medium, production increased to 3.8 mg/L. Furtherenhancement of the endogenous malonyl-CoA supply through the coexpressionof pantothenate kinase and acetyl-CoA carboxylase resulted in strainAQ-04, which produced 12.3 mg/L AQ256. Optimization of cultivationconditions enabled AQ-04 to achieve 23.9 mg/L AQ256, a 9.6-fold increasecompared to previous studies. Our results demonstrate that the combinationof introducing a malonate assimilation pathway and enhancing nativemalonyl-CoA supply is a highly effective strategy for increasing malonyl-CoAavailability. This approach is promising for the biosynthesis of awide range of malonyl-CoA-derived compounds.
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