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Exploiting marine actinomycete biosynthetic pathways for drug discovery

Antonie van Leeuwenhoek volume 87, pages 49–57 (2005)Cite this article

Abstract

Drug discovery relies on the generation of large numbers of structurally diverse compounds from which a potential candidate can be identified. To this end, actinomycetes have often been exploited because of their ability to biosynthesize an impressive array of novel metabolites particularly polyketides. The genetic organization of polyketide synthases (PKSs) makes them readily amenable to manipulation, and thus re-engineering artificial or hybrid PKSs to produce unnatural natural products is a reality. This review highlights two approaches we have used to generate novel polyketides by manipulating genes responsible for starter unit biosynthesis in the ‘Streptomyces maritimus’ enterocin type II PKS. Our preliminary investigation into the biosynthesis of neomarinone, a rare marine actinomycete-derived meroterpenoid, is also presented.

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Abbreviations

ACP:

acyl carrier protein

CoA:

coenzyme A

enc :

enterocin biosynthesis genes

FPP:

farnesyl pyrophosphate

PAL:

phenylalanine ammonia lyase

PKS:

polyketide synthase

THN:

1,3,6,8-tetrahydroxynaphthalene

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Affiliations

  1. College of Pharmacy, University of Arizona, 85721-027, Tucson, AZ, USA

    Bradley S. Moore, John A. Kalaitzis & Longkuan Xiang

  2. Department of Chemistry, University of Arizona, 85721-027, Tucson, AZ, USA

    Bradley S. Moore

Authors
  1. Bradley S. Moore
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  2. John A. Kalaitzis
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  3. Longkuan Xiang
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Correspondence to Bradley S. Moore.

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Moore, B.S., Kalaitzis, J.A. & Xiang, L. Exploiting marine actinomycete biosynthetic pathways for drug discovery. Antonie Van Leeuwenhoek 87, 49–57 (2005). https://doi.org/10.1007/s10482-004-6541-0

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  • DOI: https://doi.org/10.1007/s10482-004-6541-0

Keywords

  • Biosynthesis
  • Enterocin
  • Marine natural products
  • Meroterpenoid
  • Polyketide synthase
  • Streptomyces