Daunorubicin type II polyketide synthase enzymes DpsA and DpsB determine neither the choice of starter unit nor the cyclization pattern of aromatic polyketides

1995 ◽  
Vol 117 (21) ◽  
pp. 5899-5900 ◽  
Author(s):  
G. Meurer ◽  
C. R. Hutchinson
Keyword(s):  
Polyketide Synthase ◽  
Type Ii ◽  
Aromatic Polyketides ◽  
Starter Unit

scholarly journals Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase

2006 ◽  
Vol 72 (4) ◽  
pp. 2573-2580 ◽  
Author(s):  
Wenjun Zhang ◽  
Brian D. Ames ◽  
Shiou-Chuan Tsai ◽  
Yi Tang
Keyword(s):  
Polyketide Synthase ◽  
Major Product ◽  
Polyketide Synthases ◽  
Type Ii ◽  
Streptomyces Rimosus ◽  
Aromatic Polyketides ◽  
Starter Unit ◽  
Necessary And Sufficient ◽  
Bacterial Type

ABSTRACT Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.

scholarly journals Policing starter unit selection of the enterocin type II polyketide synthase by the type II thioesterase EncL

2011 ◽  
Vol 19 (22) ◽  
pp. 6633-6638 ◽  
Author(s):  
John A. Kalaitzis ◽  
Qian Cheng ◽  
Dario Meluzzi ◽  
Longkuan Xiang ◽  
Miho Izumikawa ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Type Ii ◽  
Unit Selection ◽  
Starter Unit ◽  
Selection Of

scholarly journals The Streptomyces peucetius dpsC Gene Determines the Choice of Starter Unit in Biosynthesis of the Daunorubicin Polyketide

1999 ◽  
Vol 181 (15) ◽  
pp. 4690-4695 ◽  
Author(s):  
Wuli Bao ◽  
Paul J. Sheldon ◽  
Evelyn Wendt-Pienkowski ◽  
C. Richard Hutchinson
Keyword(s):  
Polyketide Synthase ◽  
Primary Role ◽  
Biosynthesis Gene Cluster ◽  
Streptomyces Peucetius ◽  
Recombinant Strains ◽  
Aromatic Polyketides ◽  
Malonyl Coa ◽  
Starter Unit ◽  
Genes Encoding ◽  
A Cell

ABSTRACT The starter unit used in the biosynthesis of daunorubicin is propionyl coenzyme A (CoA) rather than acetyl-CoA, which is used in the production of most of the bacterial aromatic polyketides studied to date. In the daunorubicin biosynthesis gene cluster ofStreptomyces peucetius, directly downstream of the genes encoding the β-ketoacyl:acyl carrier protein synthase subunits, are two genes, dpsC and dpsD, encoding proteins that are believed to function as the starter unit-specifying enzymes. Recombinant strains containing plasmids carrying dpsC anddpsD, in addition to other daunorubicin polyketide synthase (PKS) genes, incorporate the correct starter unit into polyketides made by these genes, suggesting that, contrary to earlier reports, the enzymes encoded by dpsC and dpsD play a crucial role in starter unit specification. Additionally, the results of a cell-free synthesis of 21-carbon polyketides from propionyl-CoA and malonyl-CoA that used the protein extracts of recombinant strains carrying other daunorubicin PKS genes to which purified DpsC was added suggest that this enzyme has the primary role in starter unit discrimination for daunorubicin biosynthesis.

scholarly journals Aromatic polyketide biosynthesis: fidelity, evolution and engineering

2019 ◽  
Author(s):  
Zhiwei Qin ◽  
Rebecca Devine ◽  
Matthew I. Hutchings ◽  
Barrie Wilkinson
Keyword(s):  
Biosynthetic Pathway ◽  
Polyketide Synthase ◽  
Single Gene ◽  
Biosynthetic Gene Cluster ◽  
Type Ii ◽  
Trace Level ◽  
Aromatic Polyketides ◽  
Pyridine Moiety ◽  
Catalytic Role ◽  
New Compounds

AbstractWe report the formicapyridines which are structurally and biosynthetically related to the pentacyclic fasamycin and formicamycin aromatic polyketides but comprise a rare pyridine moiety. These new compounds are trace level metabolites formed by derailment of the major biosynthetic pathway. Inspired by evolutionary logic we show that rational mutation of a single gene in the biosynthetic gene cluster leads to a significant increase both in total formicapyridine production and their enrichment relative to the fasamycins/formicamycins. Our observations broaden the polyketide biosynthetic landscape and identify a non-catalytic role for ABM superfamily proteins in type II polyketide synthase assemblages for maintaining biosynthetic pathway fidelity.

scholarly journals Type II Thioesterase ScoT, Associated with Streptomyces coelicolor A3(2) Modular Polyketide Synthase Cpk, Hydrolyzes Acyl Residues and Has a Preference for Propionate

2008 ◽  
Vol 75 (4) ◽  
pp. 887-896 ◽  
Author(s):  
Magdalena Kotowska ◽  
Krzysztof Pawlik ◽  
Aleksandra Smulczyk-Krawczyszyn ◽  
Hubert Bartosz-Bechowski ◽  
Katarzyna Kuczek
Keyword(s):  
Substrate Specificity ◽  
Kinetic Parameters ◽  
Hybrid Systems ◽  
Active Site ◽  
Polyketide Synthase ◽  
Streptomyces Coelicolor ◽  
Polyketide Synthases ◽  
Type Ii ◽  
Starter Unit ◽  
Modular Polyketide Synthase

ABSTRACT Type II thioesterases (TE IIs) were shown to maintain the efficiency of polyketide synthases (PKSs) by removing acyl residues blocking extension modules. However, the substrate specificity and kinetic parameters of these enzymes differ, which may have significant consequences when they are included in engineered hybrid systems for the production of novel compounds. Here we show that thioesterase ScoT associated with polyketide synthase Cpk from Streptomyces coelicolor A3(2) is able to hydrolyze acetyl, propionyl, and butyryl residues, which is consistent with its editing function. This enzyme clearly prefers propionate, in contrast to the TE IIs tested previously, and this indicates that it may have a role in control of the starter unit. We also determined activities of ScoT mutants and concluded that this enzyme is an α/β hydrolase with Ser90 and His224 in its active site.

scholarly journals Biosynthesis of trioxacarcin revealing a different starter unit and complex tailoring steps for type II polyketide synthase

2015 ◽  
Vol 6 (6) ◽  
pp. 3440-3447 ◽  
Author(s):  
Mei Zhang ◽  
Xian-Feng Hou ◽  
Li-Hua Qi ◽  
Yue Yin ◽  
Qing Li ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Type Ii ◽  
Starter Unit

Different starter unit and complex tailoring steps for type II polyketide synthase in trioxacarcin biosynthesis.

scholarly journals Aromatic Polyketides from a Symbiotic Strain Aspergillus fumigatus D and Characterization of Their Biosynthetic Gene D8.t287

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 324
Author(s):  
Yi Hua ◽  
Rui Pan ◽  
Xuelian Bai ◽  
Bin Wei ◽  
Jianwei Chen ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Polyketide Synthase ◽  
Gene Knockout ◽  
Gene Clusters ◽  
Inhibitory Effect ◽  
Genomic Feature ◽  
Biosynthetic Gene ◽  
Aromatic Polyketides ◽  
Staphyloccocus Aureus ◽  
Coastal Plant

The chemical investigation of one symbiotic strain, Aspergillus fumigatus D, from the coastal plant Edgeworthia chrysantha Lindl led to the isolation of eight compounds (1–8), which were respectively identified as rubrofusarin B (1), alternariol 9-O-methyl ether (2), fonsecinone D (3), asperpyrone A (4), asperpyrone D (5), fonsecinone B (6), fonsecinone A (7), and aurasperone A (8) by a combination of spectroscopic methods (1D NMR and ESI-MS) as well as by comparison with the literature data. An antimicrobial assay showed that these aromatic polyketides exhibited no remarkable inhibitory effect on Escherichia coli, Staphyloccocus aureus and Candida albicans. The genomic feature of strain D was analyzed, as well as its biosynthetic gene clusters, using antibiotics and Secondary Metabolite Analysis Shell 5.1.2 (antiSMASH). Plausible biosynthetic pathways for dimeric naphtho-γ-pyrones 3–8 were first proposed in this work. A non-reducing polyketide synthase (PKS) gene D8.t287 responsible for the biosynthesis of these aromatic polyketides 1–8 was identified and characterized by target gene knockout experiment and UPLC-MS analysis.

scholarly journals Type II thioesterase ScoT is required for coelimycin production by the modular polyketide synthase Cpk of Streptomyces coelicolor A3(2).

2014 ◽  
Vol 61 (1) ◽  
Author(s):  
Magdalena Kotowska ◽  
Jarosław Ciekot ◽  
Krzysztof Pawlik
Keyword(s):  
Culture Medium ◽  
Polyketide Synthase ◽  
Streptomyces Coelicolor ◽  
Acyl Chain ◽  
No Production ◽  
Type I ◽  
Type Ii ◽  
Peptide Synthetases ◽  
Modular Polyketide Synthase ◽  
Editing Enzyme

Type II thioesterases were shown to maintain efficiency of modular type I polyketide synthases and nonribosomal peptide synthetases by removing acyl residues blocking extension modules. We found that thioesterase ScoT from Streptomyces coelicolor A3(2) is required for the production of the yellow-pigmented coelimycin by the modular polyketide synthase Cpk. No production of coelimycin was observed in cultures of scoT disruption mutant. Polyketide production was restored upon complementation with an intact copy of the scoT gene. An enzymatic assay showed that ScoT thioesterase can hydrolyse a 12-carbon acyl chain but the activity is too low to play a role in product release from the polyketide synthase. We conclude that ScoT is an editing enzyme necessary to maintain the activity of polyketide synthase Cpk. We provide a HPLC based method to measure the amount of coelimycin P2 in a culture medium.

scholarly journals The effect of divalent cations on the thermostability of type II polyketide synthase acyl carrier proteins

AIChE Journal ◽  
2018 ◽  
Vol 64 (12) ◽  
pp. 4308-4318 ◽  
Author(s):  
Marco A. Rivas ◽  
Valentine C. Courouble ◽  
Miranda C. Baker ◽  
David L. Cookmeyer ◽  
Kristen E. Fiore ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Divalent Cations ◽  
Type Ii ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins
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