Expanding the Scope of Aromatic Polyketides by Combinatorial Biosynthesis

2003 ◽  
Vol 6 (6) ◽  
pp. 501-512 ◽  
Author(s):  
J. Kantola ◽  
T. Kunnari ◽  
P. Mantsala ◽  
K. Ylihonko
Keyword(s):  
Combinatorial Biosynthesis ◽  
Aromatic Polyketides

scholarly journals Genome mining of novel rubiginones from Streptomyces sp. CB02414 and characterization of the post-PKS modification steps in rubiginone biosynthesis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingyan Zhang ◽  
Ying Sun ◽  
Yeji Wang ◽  
Xin Chen ◽  
Lu Xue ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Scale Up ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Wild Type ◽  
Aromatic Polyketides ◽  
A Genome

Abstract Background Rubiginones belong to the angucycline family of aromatic polyketides, and they have been shown to potentiate the vincristine (VCR)-induced cytotoxicity against VCR-resistant cancer cell lines. However, the biosynthetic gene clusters (BGCs) and biosynthetic pathways for rubiginones have not been reported yet. Results In this study, based on bioinformatics analysis of the genome of Streptomyces sp. CB02414, we predicted the functions of the two type II polyketide synthases (PKSs) BGCs. The rub gene cluster was predicted to encode metabolites of the angucycline family. Scale-up fermentation of the CB02414 wild-type strain led to the discovery of eight rubiginones, including five new ones (rubiginones J, K, L, M, and N). Rubiginone J was proposed to be the final product of the rub gene cluster, which features extensive oxidation on the A-ring of the angucycline skeleton. Based on the production profiles of the CB02414 wild-type and the mutant strains, we proposed a biosynthetic pathway for the rubiginones in CB02414. Conclusions A genome mining strategy enabled the efficient discovery of new rubiginones from Streptomyces sp. CB02414. Based on the isolated biosynthetic intermediates, a plausible biosynthetic pathway for the rubiginones was proposed. Our research lays the foundation for further studies on the mechanism of the cytochrome P450-catalyzed oxidation of angucyclines and for the generation of novel angucyclines using combinatorial biosynthesis strategies.

scholarly journals Assembling a plug-and-play production line for combinatorial biosynthesis of aromatic polyketides in Escherichia coli

PLoS Biology ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. e3000347 ◽  
Author(s):  
Matthew Cummings ◽  
Anna D. Peters ◽  
George F. S. Whitehead ◽  
Binuraj R. K. Menon ◽  
Jason Micklefield ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Production Line ◽  
Combinatorial Biosynthesis ◽  
Plug And Play ◽  
Aromatic Polyketides ◽  
Play Production

scholarly journals New insights into bacterial type II polyketide biosynthesis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 172 ◽  
Author(s):  
Zhuan Zhang ◽  
Hai-Xue Pan ◽  
Gong-Li Tang
Keyword(s):  
Biological Activities ◽  
Genome Mining ◽  
Large Family ◽  
Combinatorial Biosynthesis ◽  
Type Ii ◽  
Polyketide Biosynthesis ◽  
Aromatic Polyketides ◽  
Starting Point ◽  
Biosynthetic Engineering ◽  
Bacterial Type

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.

Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Test Case ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation.

scholarly journals The Combinatorial Biosynthesis of “Unnatural” Products with Polyketides

2018 ◽  
Vol 24 (6) ◽  
pp. 501-512 ◽  
Author(s):  
Chuanbo Zhang ◽  
Di Ke ◽  
Yuejiao Duan ◽  
Wenyu Lu
Keyword(s):  
Combinatorial Biosynthesis ◽  
Unnatural Products

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.

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