Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways

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 by Streptomyces 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) in Streptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs.

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Dimeric/oligomeric DNA methyltransferases: an unfinished story

Biological Chemistry ◽

10.1515/bc.2009.082 ◽

2009 ◽

Vol 390 (9) ◽

Cited By ~ 9

Author(s):

Ernst G. Malygin ◽

Alexey A. Evdokimov ◽

Stanley Hattman

Keyword(s):

Experimental Data ◽

Dna Methyltransferases ◽

Structure And Function ◽

Type I ◽

Type Ii ◽

Kinetic Characteristics ◽

Biological Substrate ◽

Oligomeric Dna ◽

And Function

Abstract DNA methyltransferases (MTases) are enzymes that carry out post-replicative sequence-specific modifications. The initial experimental data on the structure and kinetic characteristics of the EcoRI MTase led to the paradigm that type II systems comprise dimeric endonucleases and monomeric MTases. In retrospect, this was logical because, while the biological substrate of the restriction endonuclease is two-fold symmetrical, the in vivo substrate for the MTase is generally hemi-methylated and, hence, inherently asymmetric. Thus, the paradigm was extended to include all DNA MTases except the more complex bifunctional type I and type III enzymes. Nevertheless, a gradual enlightenment grew over the last decade that has changed the accepted view on the structure of DNA MTases. These results necessitate a more complex view of the structure and function of these important enzymes.

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Thermal Stability of Type II Polyketide Acyl Carrier Proteins

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.792.14 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Marco Rivas ◽

Valentine Courouble ◽

Ashley Sisto ◽

Joris Beld ◽

Bashkim Kokona ◽

...

Keyword(s):

Thermal Stability ◽

Type Ii ◽

Carrier Proteins ◽

Acyl Carrier Proteins ◽

Thermal Stability Of

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Novel Polyketide Synthase from Nectria haematococca

Applied and Environmental Microbiology ◽

10.1128/aem.70.5.2984-2988.2004 ◽

2004 ◽

Vol 70 (5) ◽

pp. 2984-2988 ◽

Cited By ~ 48

Author(s):

Stephane Graziani ◽

Christelle Vasnier ◽

Marie-Josee Daboussi

Keyword(s):

Polyketide Synthase ◽

Fungal Growth ◽

Type I ◽

Biosynthetic Pathways ◽

Carrier Proteins ◽

Nectria Haematococca ◽

Acyl Carrier Proteins ◽

Asexual Sporulation ◽

Ketoacyl Synthase ◽

Pigment Biosynthesis

ABSTRACT We identified a polyketide synthase (PKS) gene, pksN, from a strain of Nectria haematococca by complementing a mutant unable to synthesize a red perithecial pigment. pksN encodes a 2,106-amino-acid polypeptide with conserved motifs characteristic of type I PKS enzymatic domains: β-ketoacyl synthase, acyltransferase, duplicated acyl carrier proteins, and thioesterase. The pksN product groups with the Aspergillus nidulans WA-type PKSs involved in conidial pigmentation and melanin, bikaverin, and aflatoxin biosynthetic pathways. Inactivation of pksN did not cause any visible change in fungal growth, asexual sporulation, or ascospore formation, suggesting that it is involved in a specific developmental function. We propose that pksN encodes a novel PKS required for the perithecial red pigment biosynthesis.

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