Related Papers
Proceedings of the National Academy of Sciences of the United States of America
Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes
2014 •
Kaarina Sivonen
Nonribosomal peptides and polyketides are a diverse group of natural products with complex chemical structures and enormous pharmaceutical potential. They are synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we report the widespread occurrence of NRPS and PKS genetic machinery across the three domains of life with the discovery of 3,339 gene clusters from 991 organisms, by examining a total of 2,699 genomes. These gene clusters display extraordinarily diverse organizations, and a total of 1,147 hybrid NRPS/PKS clusters were found. Surprisingly, 10% of bacterial gene clusters lacked modular organization, and instead catalytic domains were mostly encoded as separate proteins. The finding of common occurrence of nonmodular NRPS differs substantially from the current classification. Sequence analysis indicates that the evolution of NRPS machineries was driven by a combination of comm...
Frontiers in Microbiology
Screening and Transcriptional Analysis of Polyketide Synthases and Non-ribosomal Peptide Synthetases in Bacterial Strains From Krubera–Voronja Cave
Ignas Kriaučiūnas
Nucleic acids research
SBSPKSv2: structure-based sequence analysis of polyketide synthases and non-ribosomal peptide synthetases
2017 •
mansi grover
Genome guided discovery of novel natural products has been a promising approach for identification of new bioactive compounds. SBSPKS web-server has been a valuable resource for analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters. We have developed an updated version - SBSPKSv2 which is based on comprehensive analysis of sequence, structure and secondary metabolite chemical structure data from 311 experimentally characterized PKS/NRPS gene clusters with known biosynthetic products. A completely new feature of SBSPKSv2 is the inclusion of features for search in chemical space. It allows the user to compare the chemical structure of a given secondary metabolite to the chemical structures of biosynthetic intermediates and final products. For identification of catalytic domains, SBSPKS now uses profile based searches, which are computationally faster and have high sensitivity. HMM profiles have also been added for a number of new domains and m...
Applied and Environmental Microbiology
Annotation of the Modular Polyketide Synthase and Nonribosomal Peptide Synthetase Gene Clusters in the Genome of Streptomyces tsukubaensis NRRL18488
2012 •
Marko Blazic, D. Goranovic
Heterologous production of polyketides by modular type I polyketide synthases in Escherichia coli
Jay D Keasling
Marine drugs
Discovery Strategies of Bioactive Compounds Synthesized by Nonribosomal Peptide Synthetases and Type-I Polyketide Synthases Derived from Marine Microbiomes
2016 •
Anargyros Chaliotis
Considering that 70% of our planet's surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolites of pharmaceutical and biotechnological interest such as nonribosomal peptides (NRPs) and polyketides (PKs) are synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSes) and type-I polyketide synthases (PKSes-I), respectively. Novel findings regarding the mechanisms underlying NRPS and PKS evolution demonstrate how microorganisms could leverage their metabolic potential. Moreover, these findings could facilitate synthetic biology approaches leading to novel bioactive compounds. Ongoing advances in bioinformatics and next-generation sequencing (NGS) technologies ...
F1000Research
New insights into bacterial type II polyketide biosynthesis
2017 •
zhuan zhang
Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984-1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds. Recently, significant advances in the structural and mechanistic identification of enzymes involved in aromatic polyketide biosynthesis have been made on the basis of novel genetic, biochemical, and chemical technologies. This review highlights the progress in bacterial type II PKSs in the past three years (2013-2016). Moreover, novel compounds discovered or created by genome mining and biosynthetic engineering are also included.
FEMS Microbiology Ecology
Polyketide synthase pathways identified from a metagenomic library are derived from soil Acidobacteria
2011 •
Kristen Becklund
BMC Bioinformatics
ASMPKS: an analysis system for modular polyketide synthases
2007 •
Kiejung Park
Background Polyketides are secondary metabolites of microorganisms with diverse biological activities, including pharmacological functions such as antibiotic, antitumor and agrochemical properties. Polyketides are synthesized by serialized reactions of a set of enzymes called polyketide synthase(PKS)s, which coordinate the elongation of carbon skeletons by the stepwise condensation of short carbon precursors. Due to their importance as drugs, the volume of data on polyketides is rapidly increasing and creating a need for computational analysis methods for efficient polyketide research. Moreover, the increasing use of genetic engineering to research new kinds of polyketides requires genome wide analysis. Results We describe a system named ASMPKS (Analysis System for Modular Polyketide Synthesis) for computational analysis of PKSs against genome sequences. It also provides overall management of information on modular PKS, including polyketide database construction, new PKS assembly, a...
Chemistry & biology
Proposed arrangement of proteins forming a bacterial type II polyketide synthase
2008 •
Sibylle Heidelberger
