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Review
.2019 May 6;7(5):124.
doi: 10.3390/microorganisms7050124.

Biosynthesis of Polyketides inStreptomyces

Affiliations
Review

Biosynthesis of Polyketides inStreptomyces

Chandra Risdian et al. Microorganisms..

Abstract

Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges.Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced byStreptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) inStreptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides inStreptomyces with three structurally-different types of PKSs.

Keywords: Streptomyces; polyketide synthases (PKSs); polyketides; secondary metabolite.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the reaction occurring in polyketide synthases (PKSs). ACP, acyl carrier protein; AT, acyltransferase; KS, ketosynthase; KR, ketoreductase; DH, dehydratase; ER, enoylreductase. Adapted with permission of Portland Press, from Vance, S.; Tkachenko, O.; Thomas, B.; Bassuni, M.; Hong, H.; Nietlispach, D.; Broadhurst, W. Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase.Biochem. J.2016,473, 1097–1110 [30].
Figure 2
Figure 2
Structure of type I PKSs with three modules and 15 domains. ACP, acyl carrier protein; AT, acyltransferase; KS, ketosynthase; KR, ketoreductase; DH, dehydratase; ER, enoylreductase.
Figure 3
Figure 3
Some of the macrolides produced byStreptomyces.
Figure 4
Figure 4
Biosynthesis of rapamycin. ACP, acyl carrier protein; AT, acyltransferase; KS, ketosynthase; KR, ketoreductase; DH, dehydratase; ER, enoylreductase; PIE, pipecolate-incorporating enzyme. Adapted with permission from Schwecke, T.; Aparicio, J.F.; Molnár, I.; König, A; Khaw, L.E.; Haydock, S.F.; Oliynyk, M.; Caffrey, P.; Cortés, J.; Lester, J.B. The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc. Natl. Acad. Sci. USA 1995, 92, 7839–7843, doi:10.1073/pnas.92.17.7839 [34]. Copyright (1995) National Academy of Sciences, U.S.A. Adapted with permission of The Royal Society of Chemistry 2001, from Staunton, J.; Weissman, K.J. Polyketide biosynthesis: A millennium review.Nat. Prod. Rep.2001,18, 380–416 [26]; permission conveyed through Copyright Clearance Center, Inc.
Figure 5
Figure 5
Some aromatic polyketides produced byStreptomyces.
Figure 6
Figure 6
Biosynthesis of doxorubicin. Adapted with permission of The Royal Society of Chemistry 2009, from Chan, Y.A.; Podevels, A.M.; Kevany, B.M.; Thomas, M.G. Biosynthesis of polyketide synthase extender units.Nat. Prod. Rep.2009,26, 90–114 [60]; permission conveyed through Copyright Clearance Center, Inc.
Figure 7
Figure 7
Some compounds produced by type III PKSs.
Figure 8
Figure 8
Biosynthesis of germicidins. Gcs: germicidin synthase. Adapted with permission from Song, L.; Barona-Gomez, F.; Corre, C.; Xiang, L.; Udwary, D.W.; Austin, M.B.; Noel, J.P.; Moore, B.S.; Challis, G.L. Type III polyketide synthase β-ketoacyl-ACP starter unit and ethylmalonyl-coA extender unit selectivity discovered by Streptomyces coelicolor genome mining.J. Am. Chem. Soc.2006,128, 14754–14755 [91]. Copyright 2006 American Chemical Society.
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