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Polyketides
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Polyketides

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (30 November 2016) | Viewed by 56793

Special Issue Editor

Prof. Dr. Kira Weissman

E-Mail Website
Guest Editor
Molecular and Structural Enzymology Group, UMR 7365 CNRS-UL, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA),, Lorraine University, Faculté de Médecine, Batiment Biopôle, 9 Avenue de la Forêt de Haye, CS 50184, 54506 Vandoeuvre-lès-Nancy, CEDEX, France
Interests: molecular enzymology; structural biology and genetic engineering of polyketide synthases (PKS) and hybrid PKS-nonribosomal peptide synthetases (NRPS)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The study of polyketide synthase (PKSs) enzymes has grown over the last quarter-century into a dynamic area, encompassing a multiplicity of complementary approaches, from metagenomics to microbiology, in vitro enzymology to structural biology, and molecular genetics to synthetic biology. A striking picture that has emerged is of the extraordinary diversity of these systems and their capacity to intersect with other types of biosynthetic pathways, even as the roles played by the polyketide metabolites for their produces remain largely obscure. This Special Issue aims to encompass papers at the forefront of research in the field, by treating in particular the following topical issues: new types of biosynthetic pathways in which PKSs are implicated; efforts to discover new polyketides by exploiting advances in genome mining (identification of novel producers, activation of silent pathways, heterologous expression, etc.); new insights into PKS function gleaned from structural biology and allied biophysical approaches; emerging information on the functions of these metabolites in the environment (chemical ecology); and novel approaches towards manipulating PKSs towards the generation of analogs for biological testing.

As Guest Editor, I cordially invite researchers to submit their work relevant to these questions to this Special Issue of Molecules.

Prof. Dr. Kira J. Weissman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biosynthesis
  • polyketide natural products
  • polyketide synthases
  • genetic engineering
  • structural biology
  • genome mining
  • chemical ecology

Published Papers (6 papers)

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Research

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2117 KiB  
Article
Functional Analysis of the Fusarielin Biosynthetic Gene Cluster
by Aida Droce, Wagma Saei, Simon Hartung Jørgensen, Reinhard Wimmer, Henriette Giese, Rasmus Dam Wollenberg, Teis Esben Sondergaard and Jens Laurids Sørensen
Molecules 2016, 21(12), 1710; https://doi.org/10.3390/molecules21121710 - 13 Dec 2016
Cited by 14 | Viewed by 6509
Abstract
Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually [...] Read more.
Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually in a Fusarium graminearum strain overexpressing the local transcription factor. The results suggest that a trans-acting enoyl reductase (FSL5) assists the polyketide synthase FSL1 in biosynthesis of a polyketide product, which is released by hydrolysis by a trans-acting thioesterase (FSL2). Deletion of the epimerase (FSL3) resulted in accumulation of an unstable compound, which could be the released product. A novel compound, named prefusarielin, accumulated in the deletion mutant of the cytochrome P450 monooxygenase FSL4. Unlike the known fusarielins from Fusarium, this compound does not contain oxygenized decalin rings, suggesting that FSL4 is responsible for the oxygenation. Full article
(This article belongs to the Special Issue Polyketides)
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1952 KiB  
Article
Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale
by Yuhong Lü, Changwu Yue, Meiyun Shao, Shengyan Qian, Ning Liu, Yuxin Bao, Miao Wang, Minghao Liu, Xiaoqian Li, Yinyin Wang and Ying Huang
Molecules 2016, 21(6), 711; https://doi.org/10.3390/molecules21060711 - 30 May 2016
Cited by 13 | Viewed by 6013
Abstract
Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B [...] Read more.
Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis. Full article
(This article belongs to the Special Issue Polyketides)
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Review

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8407 KiB  
Review
Sampling Terrestrial Environments for Bacterial Polyketides
by Patrick Hill, Graham W. Heberlig and Christopher N. Boddy
Molecules 2017, 22(5), 707; https://doi.org/10.3390/molecules22050707 - 29 Apr 2017
Cited by 10 | Viewed by 8285
Abstract
Bacterial polyketides are highly biologically active molecules that are frequently used as drugs, particularly as antibiotics and anticancer agents, thus the discovery of new polyketides is of major interest. Since the 1980s discovery of polyketides has slowed dramatically due in large part to [...] Read more.
Bacterial polyketides are highly biologically active molecules that are frequently used as drugs, particularly as antibiotics and anticancer agents, thus the discovery of new polyketides is of major interest. Since the 1980s discovery of polyketides has slowed dramatically due in large part to the repeated rediscovery of known compounds. While recent scientific and technical advances have improved our ability to discover new polyketides, one key area has been under addressed, namely the distribution of polyketide-producing bacteria in the environment. Identifying environments where producing bacteria are abundant and diverse should improve our ability to discover (bioprospect) new polyketides. This review summarizes for the bioprospector the state-of-the-field in terrestrial microbial ecology. It provides insight into the scientific and technical challenges limiting the application of microbial ecology discoveries for bioprospecting and summarizes key developments in the field that will enable more effective bioprospecting. The major recent efforts by researchers to sample new environments for polyketide discovery is also reviewed and key emerging environments such as insect associated bacteria, desert soils, disease suppressive soils, and caves are highlighted. Finally strategies for taking and characterizing terrestrial samples to help maximize discovery efforts are proposed and the inclusion of non-actinomycetal bacteria in any terrestrial discovery strategy is recommended. Full article
(This article belongs to the Special Issue Polyketides)
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6055 KiB  
Review
Towards Precision Engineering of Canonical Polyketide Synthase Domains: Recent Advances and Future Prospects
by Carmen L. Bayly and Vikramaditya G. Yadav
Molecules 2017, 22(2), 235; https://doi.org/10.3390/molecules22020235 - 05 Feb 2017
Cited by 22 | Viewed by 9866
Abstract
Modular polyketide synthases (mPKSs) build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules) of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause [...] Read more.
Modular polyketide synthases (mPKSs) build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules) of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause both unintended products and dramatically reduced activity. This limits the engineering and combinatorial potential of mPKSs, precluding access to further potential therapeutics. Different regions on a given mPKS domain determine how it interacts both with its substrate and with other domains. Within the assembly line, these interactions are crucial to the proper ordering of reactions and efficient polyketide construction. Achieving control over these domain functions, through precision engineering at key regions, would greatly expand our catalogue of accessible polyketide products. Canonical mPKS domains, given that they are among the most well-characterized, are excellent candidates for such fine-tuning. The current minireview summarizes recent advances in the mechanistic understanding and subsequent precision engineering of canonical mPKS domains, focusing largely on developments in the past year. Full article
(This article belongs to the Special Issue Polyketides)
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9927 KiB  
Review
Exploiting the Biosynthetic Potential of Type III Polyketide Synthases
by Yan Ping Lim, Maybelle K. Go and Wen Shan Yew
Molecules 2016, 21(6), 806; https://doi.org/10.3390/molecules21060806 - 22 Jun 2016
Cited by 55 | Viewed by 16379
Abstract
Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. [...] Read more.
Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development. Full article
(This article belongs to the Special Issue Polyketides)
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1496 KiB  
Review
Sorbicillinoids from Fungi and Their Bioactivities
by Jiajia Meng, Xiaohan Wang, Dan Xu, Xiaoxiang Fu, Xuping Zhang, Daowan Lai, Ligang Zhou and Guozhen Zhang
Molecules 2016, 21(6), 715; https://doi.org/10.3390/molecules21060715 - 01 Jun 2016
Cited by 70 | Viewed by 8171
Abstract
Sorbicillinoids are important hexaketide metabolites derived from fungi. They have a variety of biological activities including cytotoxic, antioxidant, antiviral and antimicrobial activity. The unique structural features of the sorbicillinoids make them attractive candidates for developing new pharmaceutical and agrochemical agents. About 90 sorbicillinoids [...] Read more.
Sorbicillinoids are important hexaketide metabolites derived from fungi. They have a variety of biological activities including cytotoxic, antioxidant, antiviral and antimicrobial activity. The unique structural features of the sorbicillinoids make them attractive candidates for developing new pharmaceutical and agrochemical agents. About 90 sorbicillinoids have been reported in the past few decades. This mini-review aims to briefly summarize their occurrence, structures, and biological activities. Full article
(This article belongs to the Special Issue Polyketides)
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