scholarly journals Inactivation of the polyketide synthase, 6-methylsalicylic acid synthase, by the specific modification of Cys-204 of the β-ketoacyl synthase by the fungal mycotoxin cerulenin

1998 ◽  
Vol 330 (2) ◽  
pp. 933-937 ◽  
Author(s):  
J. Christopher CHILD ◽  
Peter M. SHOOLINGIN-JORDAN
Keyword(s):  
Fatty Acid ◽  
Polyketide Synthase ◽  
Substrate Binding ◽  
Specific Inhibitor ◽  
Close Similarity ◽  
Type I ◽  
Specific Modification ◽  
Ketoacyl Synthase ◽  
Methylsalicylic Acid Synthase ◽  
Fatty Acid Synthases

Cerulenin, [(2S,3R)-2,3-epoxy-4-oxo-7,10-dodecadienoylamide], a mycotoxin produced by Cephalosporium caerulens, irreversibly inactivated 6-methylsalicylic acid synthase from Penicillium patulum. A combination of radiolabelling studies with [3H]cerulenin, proteolytic and chemical digestion and N-terminal sequencing of labelled peptides indicated that the site of cerulenin modification is the highly reactive substrate-binding Cys-204 of the β-ketoacyl synthase enzyme component. The thiol-specific inhibitor, iodoacetamide, was also shown to alkylate this residue. These findings are analogous with those observed for the reaction of cerulenin and iodoacetamide with type-I fatty acid synthases, demonstrating the close similarity between 6-methylsalicylic acid synthase and type-I fatty acid synthases.

scholarly journals Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase

2006 ◽  
Vol 2 (9) ◽  
pp. 494-502 ◽  
Author(s):  
Michael B Austin ◽  
Tamao Saito ◽  
Marianne E Bowman ◽  
Stephen Haydock ◽  
Atsushi Kato ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Dictyostelium Discoideum ◽  
Polyketide Synthase ◽  
Type I ◽  
Type Iii Polyketide Synthase ◽  
Type Iii ◽  
Hybrid Type ◽  
Acid Type ◽  
Fatty Acid Type

scholarly journals The architectures of iterative type I PKS and FAS

2018 ◽  
Vol 35 (10) ◽  
pp. 1046-1069 ◽  
Author(s):  
Dominik A. Herbst ◽  
Craig A. Townsend ◽  
Timm Maier
Keyword(s):  
Fatty Acid ◽  
Polyketide Synthases ◽  
Type I ◽  
Fatty Acid Synthases

The architectures of fatty acid synthases and iterative polyketide synthases are remarkably divergent despite their related biosynthetic logics.

scholarly journals Identification and functional differentiation of two type I fatty acid synthases in Brevibacterium ammoniagenes.

1996 ◽  
Vol 178 (16) ◽  
pp. 4787-4793 ◽  
Author(s):  
H P Stuible ◽  
C Wagner ◽  
I Andreou ◽  
G Huter ◽  
J Haselmann ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Functional Differentiation ◽  
Type I ◽  
Fatty Acid Synthases

Structural Similarities between 6-Methylsalicylic Acid Synthase fromPenicillium patulumand Vertebrate Type I Fatty Acid Synthase:  Evidence from Thiol Modification Studies†

Biochemistry ◽  
1996 ◽  
Vol 35 (38) ◽  
pp. 12267-12274 ◽  
Author(s):  
Christopher J. Child ◽  
Jonathan B. Spencer ◽  
Pamela Bhogal ◽  
Peter M. Shoolingin-Jordan
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Type I ◽  
Methylsalicylic Acid Synthase

scholarly journals Purification and properties of 6-methylsalicylic acid synthase from Penicillium patulum

1992 ◽  
Vol 288 (3) ◽  
pp. 839-846 ◽  
Author(s):  
J B Spencer ◽  
P M Jordan
Keyword(s):  
Fatty Acid ◽  
Proteinase Inhibitors ◽  
Type I ◽  
Acetyl Coa ◽  
Purification Method ◽  
Methylsalicylic Acid Synthase ◽  
Acid Lactone ◽  
Penicillium Patulum ◽  
Triacetic Acid Lactone

6-Methylsalicylic acid synthase has been isolated in homogeneous form from Penicillium patulum grown in liquid culture from a spore inoculum. The enzyme is highly susceptible to proteolytic degradation in vivo and in vitro, but may be stabilized during purification by incorporating proteinase inhibitors in the buffers. The enzyme exists as a homotetramer of M(r) 750,000, with a subunit M(r) of 180,000. 6-Methylsalicyclic acid synthase also accepts acetoacetyl-CoA as an alternative starter molecule to acetyl-CoA. The enzyme also catalyses the formation of small amounts of triacetic acid lactone as an oligatory by-product of the reaction. In the absence of NADPH, triacetic acid lactone is the exclusive enzymic product, being formed at 10% of the rate of 6-methylsalicylic acid. The enzyme is inactivated by 1,3-dibromopropan-2-one, leading to the formation of cross-linked dimers similar to that observed with type I fatty acid synthases. Acetyl-CoA protects the enzyme against the inactivation and inhibits dimer formation. An adaptation of the purification method for 6-methylsalicylic acid synthase may be used for the isolation of fatty acid sythase from Penicillium patulum.

scholarly journals Microbial Type I Fatty Acid Synthases (FAS): Major Players in a Network of Cellular FAS Systems

2004 ◽  
Vol 68 (3) ◽  
pp. 501-517 ◽  
Author(s):  
Eckhart Schweizer ◽  
Jörg Hofmann
Keyword(s):  
Fatty Acid ◽  
De Novo ◽  
Acid Synthesis ◽  
Chain Elongation ◽  
Type I ◽  
Mitochondrial Fatty Acid ◽  
Fatty Acid Synthases ◽  
Single Polypeptide ◽  
The Individual ◽  
Targeted Inactivation

SUMMARY The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with characteristic organization of their catalytic domains. A single polypeptide may contain one or more sets of the eight FAS component functions. Alternatively, these functions may split up into two different and mutually complementing subunits. Targeted inactivation of the individual yeast FAS acylation sites allowed us to define their roles during the overall catalytic process. In particular, their pronounced negative cooperativity is presumed to coordinate the FAS initiation and chain elongation reactions. Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline. The interplay of the involved regulatory proteins, Rap1, Reb1, Abf1, Ino2/Ino4, Opi1, Sin3 and TFIIB, has been elucidated in considerable detail. Balanced levels of subunits α and β are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits. The functional specificity of type I FAS multienzymes usually requires the presence of multiple FAS systems within the same cell. De novo synthesis of long-chain fatty acids, mitochondrial fatty acid synthesis, acylation of certain secondary metabolites and coenzymes, fatty acid elongation, and the vast diversity of mycobacterial lipids each result from specific FAS activities. The microcompartmentalization of FAS activities in type I multienzymes may thus allow for both the controlled and concerted action of multiple FAS systems within the same cell.

scholarly journals Structural insight into Pichia pastoris fatty acid synthase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph S. Snowden ◽  
Jehad Alzahrani ◽  
Lee Sherry ◽  
Martin Stacey ◽  
David J. Rowlands ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Production ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Expression System ◽  
Model Organism ◽  
Type I ◽  
Structural Insight ◽  
Fatty Acid Synthases ◽  
Insight Into

AbstractType I fatty acid synthases (FASs) are critical metabolic enzymes which are common targets for bioengineering in the production of biofuels and other products. Serendipitously, we identified FAS as a contaminant in a cryoEM dataset of virus-like particles (VLPs) purified from P. pastoris, an important model organism and common expression system used in protein production. From these data, we determined the structure of P. pastoris FAS to 3.1 Å resolution. While the overall organisation of the complex was typical of type I FASs, we identified several differences in both structural and enzymatic domains through comparison with the prototypical yeast FAS from S. cerevisiae. Using focussed classification, we were also able to resolve and model the mobile acyl-carrier protein (ACP) domain, which is key for function. Ultimately, the structure reported here will be a useful resource for further efforts to engineer yeast FAS for synthesis of alternate products.

scholarly journals Novel Polyketide Synthase from Nectria haematococca

2004 ◽  
Vol 70 (5) ◽  
pp. 2984-2988 ◽  
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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