Polyketide synthase com plexes: their structure and function in antibiotic biosynthesis

1991 ◽  
Vol 332 (1263) ◽  
pp. 107-114 ◽  
Keyword(s):  
Structural Organization ◽  
Polyketide Synthase ◽  
Structure And Function ◽  
Polyketide Synthases ◽  
Antibiotic Biosynthesis ◽  
Homologous Region ◽  
Polyketide Biosynthesis ◽  
Monensin A ◽  
And Function ◽  
Spore Pigment

This paper gives an overview of existing knowledge concerning the structure and deduced functions of polyketide synthases active in antibiotic-producing streptomycetes. Using monensin A as an example of a structurally complex polyketide metabolite, the problem of understanding how individual strains of microorganism are ‘programmed’ to produce a given polyketide metabolite is first outlined. The question then arises, how is the programming of polyketide assembly related to the structural organization of individual polyketide synthase complexes at the biochemical and genetic levels? Experimental results that help to illuminate these relations are described, in particular, those giving information about the structures and deduced functions of polyketide synthases involved in aromatic polyketide biosynthesis (actinorhodin, granaticin, tetracenomycin, whiE spore pigment and an act homologous region from the monensin-producing organism), as well as the macrolide polyketide synthase active in the biosynthesis of 6-deoxyerythronolide A.

Polyketide Synthase: Sequence, Structure, and Function

2014 ◽  
pp. 219-243 ◽  
Author(s):  
Joel Bruegger ◽  
Grace Caldara ◽  
Joris Beld ◽  
Michael D. Burkart ◽  
Shiou-Chuan Sheryl Tsai
Keyword(s):  
Polyketide Synthase ◽  
Structure And Function ◽  
Sequence Structure ◽  
And Function

scholarly journals Structural Organization of Procaryotic and Eucaryotic Hsp90. INFLUENCE OF DIVALENT CATIONS ON STRUCTURE AND FUNCTION

1995 ◽  
Vol 270 (24) ◽  
pp. 14412-14419 ◽  
Author(s):  
Ursula Jakob ◽  
Ines Meyer ◽  
Hans Bügl ◽  
Stefanie André ◽  
James C. A. Bardwell ◽  
...  
Keyword(s):  
Structural Organization ◽  
Divalent Cations ◽  
Structure And Function ◽  
And Function

scholarly journals Insertional Inactivation of Methylmalonyl Coenzyme A (CoA) Mutase and Isobutyryl-CoA Mutase Genes in Streptomyces cinnamonensis: Influence on Polyketide Antibiotic Biosynthesis

1999 ◽  
Vol 181 (18) ◽  
pp. 5600-5605 ◽  
Author(s):  
Jan W. Vrijbloed ◽  
Katja Zerbe-Burkhardt ◽  
Ananda Ratnatilleke ◽  
Andreas Grubelnik-Leiser ◽  
John A. Robinson
Keyword(s):  
Sole Carbon Source ◽  
Coenzyme A ◽  
Carbon Sources ◽  
Antibiotic Biosynthesis ◽  
Polyketide Biosynthesis ◽  
Streptomyces Cinnamonensis ◽  
Insertional Inactivation ◽  
Hygromycin Resistance Gene ◽  
Monensin A ◽  
Coenzyme B

ABSTRACT The coenzyme B12-dependent isobutyryl coenzyme A (CoA) mutase (ICM) and methylmalonyl-CoA mutase (MCM) catalyze the isomerization of n-butyryl-CoA to isobutyryl-CoA and of methylmalonyl-CoA to succinyl-CoA, respectively. The influence that both mutases have on the conversion of n- and isobutyryl-CoA to methylmalonyl-CoA and the use of the latter in polyketide biosynthesis have been investigated with the polyether antibiotic (monensin) producer Streptomyces cinnamonensis. Mutants prepared by inserting a hygromycin resistance gene (hygB) into either icmA or mutB, encoding the large subunits of ICM and MCM, respectively, have been characterized. The icmA::hygB mutant was unable to grow on valine or isobutyrate as the sole carbon source but grew normally on butyrate, indicating a key role for ICM in valine and isobutyrate metabolism in minimal medium. ThemutB::hygB mutant was unable to grow on propionate and grew only weakly on butyrate and isobutyrate as sole carbon sources. 13C-labeling experiments show that in both mutants butyrate and acetoacetate may be incorporated into the propionate units in monensin A without cleavage to acetate units. Hence, n-butyryl-CoA may be converted into methylmalonyl-CoA through a carbon skeleton rearrangement for which neither ICM nor MCM alone is essential.

scholarly journals Biosynthesis of Polyketides in Streptomyces

2019 ◽  
Vol 7 (5) ◽  
pp. 124 ◽  
Author(s):  
Chandra Risdian ◽  
Tjandrawati Mozef ◽  
Joachim Wink
Keyword(s):  
Secondary Metabolites ◽  
Structure And Function ◽  
Polyketide Synthases ◽  
Type I ◽  
Type Ii ◽  
Filamentous Form ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Different Types ◽  
And Function

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.

From Beads on a String to the Pearls of Regulation: the Structure and Dynamics of Chromatin

2012 ◽  
Vol 40 (2) ◽  
pp. 331-334
Author(s):  
Richard P. Bowater ◽  
Ian C. Wood ◽  
Ben F. Luisi
Keyword(s):  
Structural Biology ◽  
Structural Organization ◽  
Regulation Of Gene Expression ◽  
Structure And Function ◽  
Research Field ◽  
Structure And Dynamics ◽  
Recent Conference ◽  
Eukaryotic Chromatin ◽  
Poster Presentations ◽  
And Function

The assembly of eukaryotic chromatin, and the bearing of its structural organization on the regulation of gene expression, were the central topics of a recent conference organized jointly by the Biochemical Society and Wellcome Trust. A range of talks and poster presentations covered topical aspects of this research field and illuminated recent advances in our understanding of the structure and function of chromatin. The two-day meeting had stimulating presentations complemented with lively discourse and interactions of participants. In the present paper, we summarize the topics presented at the meeting, in particular highlighting subjects that are reviewed in more detail within this issue of Biochemical Society Transactions. The reports bring to life the truly fascinating molecular and structural biology of chromatin.

scholarly journals Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Edward Kalkreuter ◽  
Kyle S. Bingham ◽  
Aaron M. Keeler ◽  
Andrew N. Lowell ◽  
Jennifer J. Schmidt ◽  
...  
Keyword(s):  
Active Site ◽  
Polyketide Synthase ◽  
Polyketide Synthases ◽  
Substrate Selectivity ◽  
Substrate Selection ◽  
Polyketide Biosynthesis ◽  
Erythromycin Biosynthesis ◽  
Malonyl Coa ◽  
Modular Polyketide Synthase ◽  
Dynamics Simulations

AbstractPolyketides, one of the largest classes of natural products, are often clinically relevant. The ability to engineer polyketide biosynthesis to produce analogs is critically important. Acyltransferases (ATs) of modular polyketide synthases (PKSs) catalyze the installation of malonyl-CoA extenders into polyketide scaffolds. ATs have been targeted extensively to site-selectively introduce various extenders into polyketides. Yet, a complete inventory of AT residues responsible for substrate selection has not been established, limiting the scope of AT engineering. Here, molecular dynamics simulations are used to prioritize ~50 mutations within the active site of EryAT6 from erythromycin biosynthesis, leading to identification of two previously unexplored structural motifs. Exchanging both motifs with those from ATs with alternative extender specificities provides chimeric PKS modules with expanded and inverted substrate specificity. Our enhanced understanding of AT substrate selectivity and application of this motif-swapping strategy are expected to advance our ability to engineer PKSs towards designer polyketides.

Sign in / Sign up

Export Citation Format

Share Document