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Antibiotics 2018, 7(3), 62; https://doi.org/10.3390/antibiotics7030062

Acyltransferases as Tools for Polyketide Synthase Engineering

Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany
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Received: 2 June 2018 / Revised: 14 July 2018 / Accepted: 16 July 2018 / Published: 18 July 2018
(This article belongs to the Special Issue Actinomycetes: The Antibiotics Producers)
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Abstract

Polyketides belong to the most valuable natural products, including diverse bioactive compounds, such as antibiotics, anticancer drugs, antifungal agents, immunosuppressants and others. Their structures are assembled by polyketide synthases (PKSs). Modular PKSs are composed of modules, which involve sets of domains catalysing the stepwise polyketide biosynthesis. The acyltransferase (AT) domains and their “partners”, the acyl carrier proteins (ACPs), thereby play an essential role. The AT loads the building blocks onto the “substrate acceptor”, the ACP. Thus, the AT dictates which building blocks are incorporated into the polyketide structure. The precursor- and occasionally the ACP-specificity of the ATs differ across the polyketide pathways and therefore, the ATs contribute to the structural diversity within this group of complex natural products. Those features make the AT enzymes one of the most promising tools for manipulation of polyketide assembly lines and generation of new polyketide compounds. However, the AT-based PKS engineering is still not straightforward and thus, rational design of functional PKSs requires detailed understanding of the complex machineries. This review summarizes the attempts of PKS engineering by exploiting the AT attributes for the modification of polyketide structures. The article includes 253 references and covers the most relevant literature published until May 2018. View Full-Text
Keywords: natural products; polyketides; polyketide synthases; acyltransferases; engineering; new bioactive compounds natural products; polyketides; polyketide synthases; acyltransferases; engineering; new bioactive compounds
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Musiol-Kroll, E.M.; Wohlleben, W. Acyltransferases as Tools for Polyketide Synthase Engineering. Antibiotics 2018, 7, 62.

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