ArticleACS chemical biology2018
Extender Unit Promiscuity and Orthogonal Protein Interactions of an Aminomalonyl-ACP Utilizing Trans-Acyltransferase from Zwittermicin Biosynthesis.
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 5 papers.
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Who cites it
5 citing papers in PubMed.
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Current State-of-the-Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products.Chembiochem : a European journal of chemical biology · 2023Review
- Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase.Nature communications · 2021Article
- Synthetic biology enabling access to designer polyketides.Current opinion in chemical biology · 2020Review
- Engineering actinomycetes for biosynthesis of macrolactone polyketides.Microbial cell factories · 2019Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Trans-acting acyltransferases (trans-ATs) are standalone enzymes that select and deliver extender units to polyketide synthase assembly lines. Accordingly, there is interest in leveraging trans-ATs as tools to regioselectively diversify polyketide structures. Yet, little is known regarding the extender unit and acyl carrier protein (ACP) specificity of trans-ATs, particularly those that utilize unusual ACP-linked extender units. For example, the biosynthesis of the antibiotic zwittermicin involves the trans-AT ZmaF, which is responsible for installing a rare ACP-linked aminomalonyl extender unit. Here, we developed a method to access a panel of non-natural and non-native ACP-linked extender units and used it to probe the promiscuity of ZmaF, revealing one of the most promiscuous ATs characterized to date. Furthermore, we demonstrated that ZmaF is highly orthogonal with respect to its ACP specificity, and the ability of ZmaF to trans-complement noncognate PKS modules was also explored. Together, these results set the stage for further engineering ZmaF as a tool for polyketide diversification.
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Registered trials
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