ArticleACS chemical biology2018
De Novo Design and Implementation of a Tandem Acyl Carrier Protein Domain in a Type I Modular Polyketide Synthase.
Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 14 citations in OpenAlex.
- Structural and dynamic roles of tandem acyl carrier proteins in aryl polyene biosynthesis in carbapenem-resistant Acinetobacter baumannii.Protein science : a publication of the Protein Society · 2025Article
- Divergent Tandem Acyl Carrier Proteins Necessitate In-Series Polyketide Processing in the Leinamycin Family.Angewandte Chemie (International ed. in English) · 2025Article
- Modular polyketide synthase contains two reaction chambers that operate asynchronously.Science (New York, N.Y.) · 2021Article
- Synthetic biology enabling access to designer polyketides.Current opinion in chemical biology · 2020Review
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
During polyketide and fatty acid biosynthesis, the growing acyl chain is attached to the acyl carrier protein via a thioester linkage. The acyl carrier protein interacts with other enzymes that perform chain elongation and chain modification on the bound acyl chain. Most type I polyketide synthases and fatty acid synthases contain only one acyl carrier protein. However, polyunsaturated fatty acid synthases from deep-sea bacteria contain anywhere from two to nine acyl carrier proteins. Recent studies have shown that this tandem acyl carrier protein feature is responsible for the unusually high fatty acid production rate of deep-sea bacteria. To investigate if a similar strategy can be used to increase the production rate of type I polyketide synthases, a 3×ACP domain was rationally designed and genetically installed in module 6 of 6-deoxyerythronolide B synthase, which is a prototypical type I modular polyketide synthase that naturally harbors just one acyl carrier protein. This modification resulted in an ∼2.5-fold increase in the total amount of polyketide produced in vitro, demonstrating that installing a tandem acyl carrier domain in a type I polyketide synthase is an effective strategy for enhancing the rate of polyketide natural product biosynthesis.
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Registered trials
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