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Genetic engineering of macrolide biosynthesis: past advances, current state, and future prospects

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Abstract

Polyketides comprise one of the major families of natural products. They are found in a wide variety of bacteria, fungi, and plants and include a large number of medically important compounds. Polyketides are biosynthesized by polyketide synthases (PKSs). One of the major groups of polyketides are the macrolides, the activities of which are derived from the presence of a macrolactone ring to which one or more 6-deoxysugars are attached. The core macrocyclic ring is biosynthesized from acyl-CoA precursors by PKS. Genetic manipulation of PKS-encoding genes can result in predictable changes in the structure of the macrolactone component, many of which are not easily achieved through standard chemical derivatization or total synthesis. Furthermore, many of the changes, including post-PKS modifications such as glycosylation and oxidation, can be combined for further structural diversification. This review highlights the current state of novel macrolide production with a focus on the genetic engineering of PKS and post-PKS tailoring genes. Such engineering of the metabolic pathways for macrolide biosynthesis provides attractive alternatives for the production of diverse non-natural compounds. Other issues of importance, including the engineering of precursor pathways and heterologous expression of macrolide biosynthetic genes, are also considered.

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Acknowledgement

The work performed in the authors' laboratory and summarized in this article was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST; R0A-2008-000-20030-0, 2009K000712), Seoul R&BD Program grant (KU080657M0209721), and the Marine and Extreme Genome Research Center Program of the Ministry of Land, Transportation, and Maritime Affairs, Republic of Korea.

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  1. Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea

    Sung Ryeol Park, Yeon-Hee Ban, Young Ji Yoo, Eun Ji Kim & Yeo Joon Yoon

  2. Interdisciplinary Program of Bioengineering, Seoul National University, Seoul, 151-742, Republic of Korea

    Ah Reum Han

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  1. Sung Ryeol Park
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  4. Young Ji Yoo
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  6. Yeo Joon Yoon
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Correspondence to Yeo Joon Yoon.

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Park, S.R., Han, A.R., Ban, YH. et al. Genetic engineering of macrolide biosynthesis: past advances, current state, and future prospects. Appl Microbiol Biotechnol 85, 1227–1239 (2010). https://doi.org/10.1007/s00253-009-2326-8

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  • DOI: https://doi.org/10.1007/s00253-009-2326-8

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