ArticleMicrobial biotechnology2022
Redirection of acyl donor metabolic flux for lipopeptide A40926B0 biosynthesis.
Article in Microbial biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Strategy for enhanced production of A40926B0 inSynthetic and systems biotechnology · 2027Article
- Production improvement of dalbavancin precursor A40926B0 inSynthetic and systems biotechnology · 2027Article
- A three-plasmid-containing CRISPR-Cas9 platform to engineerApplied and environmental microbiology · 2025Article
- Expanding catalytic versatility of modular polyketide synthases for alcohol biosynthesis.Nature chemical biology · 2025Article
- A new paradigm for the regulation of A40926B0 biosynthesis.Synthetic and systems biotechnology · 2025Article
- Redirection of acyl donor metabolic flux for lipopeptide A40926B0 biosynthesis.Microbial biotechnology · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metabolic flux of fatty acyl-CoAs determines lipopeptide biosynthesis efficiency, because acyl donor competition often occurs from polyketide biosynthesis and homologous pathways. We used A40926B0 as a model to investigate this mechanism. The lipopeptide A40926B0 with a fatty acyl group is the active precursor of dalbavancin, which is considered as a new lipoglycopeptide antibiotic. The biosynthetic pathway of fatty acyl-CoAs in the A40926B0 producer Nonomuraea gerenzanensis L70 was efficiently engineered using endogenous replicon CRISPR (erCRISPR). A polyketide pathway and straight-chain fatty acid biosynthesis were identified as major competitors in the malonyl-CoA pool. Therefore, we modified both pathways to concentrate acyl donors for the production of the desired compound. Combined with multiple engineering approaches, including blockage of an acetylation side reaction, overexpression of acetyl-CoA carboxylase, duplication of the dbv gene cluster and optimization of the fermentation parameters, the final strain produced 702.4 mg l
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