scholarly journals DDAP: docking domain affinity and biosynthetic pathway prediction tool for type I polyketide synthases

2019 ◽  
Author(s):  
Tingyang Li ◽  
Ashootosh Tripathi ◽  
Fengan Yu ◽  
David H. Sherman ◽  
Arvind Rao
Keyword(s):  
Polyketide Synthase ◽  
High Efficiency ◽  
Prediction Algorithm ◽  
Type I ◽  
Biosynthetic Pathways ◽  
Data Set ◽  
Link Type ◽  
Pathway Prediction ◽  
Modular Polyketide Synthase ◽  
Popular Rule

AbstractSummaryDDAP is a tool for predicting the biosynthetic pathways of the products of type I modular polyketide synthase (PKS) with the focus on providing a more accurate prediction of the ordering of proteins and substrates in the pathway. In this study, the module docking domain (DD) affinity prediction performance on a hold-out testing data set reached AUC = 0.88; the MRR of pathway prediction reached 0.67. DDAP has advantages compared to previous informatics tools in several aspects: (i) it does not rely on large databases, making it a high efficiency tool, (ii) the predicted DD affinity is represented by a probability (0 to 1), which is more intuitive than raw scores, (iii) its performance is competitive compared to the current popular rule-based algorithm. To the best of our knowledge, DDAP is so far the first machine learning based algorithm for type I PKS pathway prediction. We also established the first database of type I modular PKSs, featuring a comprehensive annotation of available docking domains information in bacterial biosynthetic pathways.Availability and implementationThe DDAP database is available at https://tylii.github.io/ddap. The prediction algorithm DDAP is freely available on GitHub (https://github.com/tylii/ddap) and released under the MIT [email protected]

scholarly journals DDAP: docking domain affinity and biosynthetic pathway prediction tool for type I polyketide synthases

2019 ◽  
Author(s):  
Tingyang Li ◽  
Ashootosh Tripathi ◽  
Fengan Yu ◽  
David H Sherman ◽  
Arvind Rao
Keyword(s):  
Polyketide Synthase ◽  
High Efficiency ◽  
Supplementary Information ◽  
Prediction Algorithm ◽  
Type I ◽  
Biosynthetic Pathways ◽  
Testing Dataset ◽  
Pathway Prediction ◽  
Modular Polyketide Synthase ◽  
Popular Rule

Abstract Summary DDAP is a tool for predicting the biosynthetic pathways of the products of type I modular polyketide synthase (PKS) with the focus on providing a more accurate prediction of the ordering of proteins and substrates in the pathway. In this study, the module docking domain (DD) affinity prediction performance on a hold-out testing dataset reached 0.88 as measured by the area under the receiver operating characteristic (ROC) curve (AUC); the Mean Reciprocal Ranking (MRR) of pathway prediction reached 0.67. DDAP has advantages compared to previous informatics tools in several aspects: (i) it does not rely on large databases, making it a high efficiency tool, (ii) the predicted DD affinity is represented by a probability (0–1), which is more intuitive than raw scores, (iii) its performance is competitive compared to the current popular rule-based algorithm. DDAP is so far the first machine learning based algorithm for type I PKS DD affinity and pathway prediction. We also established the first database of type I modular PKSs, featuring a comprehensive annotation of available docking domains information in bacterial biosynthetic pathways. Availability and implementation The DDAP database is available at https://tylii.github.io/ddap. The prediction algorithm DDAP is freely available on GitHub (https://github.com/tylii/ddap) and released under the MIT license. Supplementary information Supplementary data are available at Bioinformatics online.

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 ClusterCAD: a computational platform for type I modular polyketide synthase design

2017 ◽  
Vol 46 (D1) ◽  
pp. D509-D515 ◽  
Author(s):  
Clara H Eng ◽  
Tyler W H Backman ◽  
Constance B Bailey ◽  
Christophe Magnan ◽  
Héctor García Martín ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Type I ◽  
Modular Polyketide Synthase ◽  
Computational Platform

scholarly journals A New Clustering and Nomenclature for Beta Turns Derived from High-Resolution Protein Structures

2018 ◽  
Author(s):  
Maxim Shapovalov ◽  
Slobodan Vucetic ◽  
Roland L. Dunbrack
Keyword(s):  
Protein Structure ◽  
High Resolution ◽  
Protein Structures ◽  
Protein Structure Determination ◽  
Classical Type ◽  
Type I ◽  
Beta Turns ◽  
Data Set ◽  
Beta Turn ◽  
Link Type

AbstractProtein loops connect regular secondary structures and contain 4-residue beta turns which represent 63% of the residues in loops. The commonly used classification of beta turns (Type I, I’, II, II’, VIa1, VIa2, VIb, and VIII) was developed in the 1970s and 1980s from analysis of a small number of proteins of average resolution, and represents only two thirds of beta turns observed in proteins (with a generic class Type IV representing the rest). We present a new clustering of beta turn conformations from a set of 13,030 turns from 1078 ultra-high resolution protein structures (≤1.2 Å). Our clustering is derived from applying the DBSCAN andk-medoids algorithms to this data set with a metric commonly used in directional statistics applied to the set of dihedral angles from the second and third residues of each turn. We define 18 turn types compared to the 8 classical turn types in common use. We propose a new 2-letter nomenclature for all 18 beta-turn types using Ramachandran region names for the two central residues (e.g., ‘A’ and ‘D’ for alpha regions on the left side of the Ramachandran map and ‘a’ and ‘d’ for equivalent regions on the right-hand side; classical Type I turns are ‘AD’ turns and Type I’ turns are ‘ad’). We identify 11 new types of beta turn, 5 of which are sub-types of classical beta turn types. Up-to-date statistics, probability densities of conformations, and sequence profiles of beta turns in loops were collected and analyzed. A library of turn types,BetaTurnLib18, and cross-platform software,BetaTurnTool18, which identifies turns in an input protein structure, are freely available and redistributable fromdunbrack.fccc.edu/betaturnandgithub.com/sh-maxim/BetaTurn18. Given the ubiquitous nature of beta turns, this comprehensive study updates understanding of beta turns and should also provide useful tools for protein structure determination, refinement, and prediction programs.

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.

scholarly journals PCR Detection of Type I Polyketide Synthase Genes in Myxobacteria

2008 ◽  
Vol 74 (17) ◽  
pp. 5571-5574 ◽  
Author(s):  
Hisayuki Komaki ◽  
Ryosuke Fudou ◽  
Takashi Iizuka ◽  
Daisuke Nakajima ◽  
Koei Okazaki ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Pcr Amplification ◽  
Pcr Detection ◽  
Type I ◽  
Dna Encoding ◽  
Modular Polyketide Synthase

ABSTRACT The diversity of type I modular polyketide synthase (PKS) was explored by PCR amplification of DNA encoding ketosynthase and acyltransferase domains in myxobacteria. The sequencing of the amplicons revealed that many PKS genes were distantly related to the published sequences. Thus, myxobacteria may be excellent resources for novel and diverse polyketides.

scholarly journals Post-PKS Tailoring Steps of the Spiramycin Macrolactone Ring in Streptomyces ambofaciens

2013 ◽  
Vol 57 (8) ◽  
pp. 3836-3842 ◽  
Author(s):  
Hoang-Chuong Nguyen ◽  
Emmanuelle Darbon ◽  
Robert Thai ◽  
Jean-Luc Pernodet ◽  
Sylvie Lautru
Keyword(s):  
Polyketide Synthase ◽  
Keto Group ◽  
Hydroxyl Group ◽  
Type I ◽  
Content Type ◽  
Methyl Group ◽  
Group Reduction ◽  
Streptomyces Ambofaciens ◽  
Modular Polyketide Synthase ◽  
Biosynthetic Studies

ABSTRACTSpiramycins are clinically important 16-member macrolide antibiotics produced byStreptomyces ambofaciens. Biosynthetic studies have established that the earliest lactonic intermediate in spiramycin biosynthesis, the macrolactone platenolide I, is synthesized by a type I modular polyketide synthase (PKS). Platenolide I then undergoes a series of post-PKS tailoring reactions yielding the final products, spiramycins I, II, and III. We recently characterized the post-PKS glycosylation steps of spiramycin biosynthesis inS. ambofaciens. We showed that three glycosyltransferases, Srm5, Srm29, and Srm38, catalyze the successive attachment of the three carbohydrates mycaminose, forosamine, and mycarose, respectively, with the help of two auxiliary proteins, Srm6 and Srm28. However, the enzymes responsible for the other tailoring steps, namely, the C-19 methyl group oxidation, the C-9 keto group reduction, and the C-3 hydroxyl group acylation, as well as the timing of the post-PKS tailoring reactions, remained to be established. In this study, we show that Srm13, a cytochrome P450, catalyzes the oxidation of the C-19 methyl group into a formyl group and that Srm26 catalyzes the reduction of the C-9 keto group, and we propose a timeline for spiramycin-biosynthetic post-PKS tailoring reactions.

Alteration of Polyketide Stereochemistry from anti to syn by a Ketoreductase Domain Exchange in a Type I Modular Polyketide Synthase Subunit

Biochemistry ◽  
2016 ◽  
Vol 55 (12) ◽  
pp. 1677-1680 ◽  
Author(s):  
Clara H. Eng ◽  
Satoshi Yuzawa ◽  
George Wang ◽  
Edward E. K. Baidoo ◽  
Leonard Katz ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Type I ◽  
Modular Polyketide Synthase
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