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 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 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 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

scholarly journals Engineering Anthracycline Biosynthesis toward Angucyclines

2003 ◽  
Vol 47 (4) ◽  
pp. 1291-1296 ◽  
Author(s):  
Mikko Metsä-Ketelä ◽  
Kaisa Palmu ◽  
Tero Kunnari ◽  
Kristiina Ylihonko ◽  
Pekka Mäntsälä
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Gene Cassette ◽  
Side Chain ◽  
Antibiotic Biosynthesis ◽  
Biosynthesis Gene Cluster ◽  
Biosynthesis Gene ◽  
Starter Unit

ABSTRACT The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin and its precursor, UWM6. Substrate flexibility of pgaF was demonstrated by replacement of the nogalamycin minimal polyketide synthase genes in the gene cassette with the equivalent aclacinomycin genes together with aknE2 and aknF, which specify the unusual propionate starter unit in aclacinomycin biosynthesis. This modification led to the production of a novel angucyclinone, MM2002, in which the expected ethyl side chain was incorporated into the fourth ring.

Bacterial Diversity and Phylogenetic Analysis of Type II Polyketide Synthase Gene from Manao-Pee Cave, Thailand

2018 ◽  
Vol 35 (6) ◽  
pp. 518-527 ◽  
Author(s):  
Apirak Wiseschart ◽  
Wuttichai Mhuanthong ◽  
Pattamaporn Thongkam ◽  
Sithichoke Tangphatsornruang ◽  
Duriya Chantasingh ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Bacterial Diversity ◽  
Polyketide Synthase ◽  
Type Ii ◽  
Polyketide Synthase Gene
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