Phage P1-Derived Artificial Chromosomes Facilitate Heterologous Expression of the FK506 Gene Cluster

Jones, Adam C.; Gust, Bertolt; Kulik, Andreas; Heide, Lutz; Buttner, Mark J.; Bibb, Mervyn J.

doi:10.1371/journal.pone.0069319

Cited by 80 publications

(69 citation statements)

References 52 publications

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“…To validate this hypothesis, the BGC coding for valinomycin biosynthesis was screened from a Streptomyces sp. CBMAI 2042 genomic library and the resulting pESAC13A derivative vector (PAC4H), containing the whole vlm gene cluster, was transferred by conjugation to S. coelicolor M1146 (Figure S5 and S6). The recombinant strain M1146/PAC4H#5 DSM 32578 (R. Sigrist, L. Gonzaga de Oliveira, 23 August 2017, Brazilian patent application BR1020170130239) reconstituted valinomycin and montanastatin production, supporting the hypothesis that both metabolites share a common biosynthetic origin.…”

Section: Figurementioning

confidence: 99%

New Cyclodepsipeptide Derivatives Revealed by Genome Mining and Molecular Networking

et al. 2019

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Genome mining and molecular networking analyses have revealed a renewed capacity to uncover molecules and biosynthetic pathways from bacterial secondary metabolism. The present study describes the association of genome mining and molecular networking to correlate production of valinomycin cyclodepsipeptide derivatives by Streptomyces sp. CBMAI 2042. Additionally, expression of the entire gene cluster in a heterologous host successfully allowed the association of this biosynthetic assembly to the production of montanastatin, valinomycin and at least five structural analogues, revealing a plasticity of the modules and an interesting thioesterase activity capable of assembling two or three units of the tetradepsipeptide monomer.

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Section: Figurementioning

confidence: 99%

New Cyclodepsipeptide Derivatives Revealed by Genome Mining and Molecular Networking

et al. 2019

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“…To facilitate analysis of the role of SalE, and future manipulation of salinomycin biosynthesis, we undertook transplantation of the entire salinomycin gene cluster (Figures S18 and S19) as a single 136.8 kbp region of S. albus DNA into Streptomyces coelicolor M1154, a heterologous host strain producing no significant polyketide natural products of its own 17. A large‐insert P1‐based artificial chromosome (PAC) library in Escherichia coli was screened for the presence of the sal genes, and one positive PAC clone was selected, characterized and transferred by conjugation into S. coelicolor M1154 (Supporting Information and Figure S20) 18. HPLC‐MS analysis of the recombinant strain confirmed the production of authentic salinomycin at levels (≈2.4 mg mL −1 ) around 10 % of those typically seen from wild‐type S. albus (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

High‐Performance Polymers from Nature: Catalytic Routes and Processes for Industry

Walther

2014

ChemSusChem

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It is difficult to imagine life today without polymers. However, most chemicals are almost exclusively synthesized from petroleum. With diminishing oil reserves, establishing an industrial process to transform renewables into high-value chemicals may be more challenging than running a car without gasoline. This is due to the difficulty in setting up processes that are novel, profitable, and environmentally benign at the same time. Additionally, the quest for sustainability of renewable resources should be based on incorporating ethical considerations in the development of plans that utilize feedstocks intended for human nutrition and health. Thus, it is important to use bio-energy containing renewable resources in the most efficient way. This Concept goes beyond the synthesis of monomers and provides insights for establishing an industrial process that transforms renewable resources into high-value chemicals, and it describes careful investigations that are of paramount importance, including evaluations from an economical and an ecological perspective. The synthesis of monomers suitable for polymer production from renewable resources would ideally be accompanied by a reduction in CO2 emission and waste, through the complete molecular utilization of the feedstock. This Concept advocates the drop-in strategy, and is guided by the example of catalytically synthesized dimethyl 1,19-nonadecanedioate and its α,ω-functionalized derivatives. With respect to the Twelve Principles of Green Chemistry, this Concept describes a technological leap forward for a sustainable green chemical industry.

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“…Direct capture of BGCs and the use of transformation-associated- recombination (TAR) identified cosmomycin (Figure 2) and its analogues, and ammosamides A-C in the culture of recombinant S. coelicolor strains (Jordan and Moore, 2016; Larson et al, 2017). Following the cloning of gene cluster from S. tsukubaensis NRRL 18444 using a P1-derived artificial chromosome (PAC) expression vector, Bibb and his colleagues heterologously expressed the 83.5-kb FK506 gene cluster in a few S. coelicolor hosts (Jones et al, 2013); the yield of FK506 was increased from 1.2 mg/L to 5.5 mg/L in M1146 when the LuxR regulatory gene fkbN was over-expressed. Using the same PAC vector system, neoabyssomicin A/B and abyssomicin 2/4 were recently identified from a deep-sea isolate S. koyangensis SCSIO 5802 via expressing PAC constructs heterologously in M1152 (Tu et al, 2018).…”

Section: Streptomyces Coelicolor As a Heterologous Hostmentioning

confidence: 99%

Streptomycetes: Surrogate hosts for the genetic manipulation of biosynthetic gene clusters and production of natural products

Nepal

Wang

2019

Biotechnology Advances

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Due to the worldwide prevalence of multidrug-resistant pathogens and high incidence of diseases such as cancer, there is an urgent need for the discovery and development of new drugs. Nearly half of the FDA-approved drugs are derived from natural products that are produced by living organisms, mainly bacteria, fungi, and plants. Commercial development is often limited by the low yield of the desired compounds expressed by the native producers. In addition, recent advances in whole genome sequencing and bioinformatics have revealed an abundance of cryptic biosynthetic gene clusters within microbial genomes. Genetic manipulation of clusters in the native host is commonly used to awaken poorly expressed or silent gene clusters, however, the lack of feasible genetic manipulation systems in many strains often hinders our ability to engineer the native producers. The transfer of gene clusters into heterologous hosts for expression of partial or entire biosynthetic pathways is an approach that can be used to overcome this limitation. Heterologous expression also facilitates the chimeric fusion of different biosynthetic pathways, leading to the generation of “unnatural” natural products. The genus Streptomyces is especially known to be a prolific source of drugs/antibiotics, its members are often used as heterologous expression hosts. In this review, we summarize recent applications of Streptomyces species, S. coelicolor, S. lividans, S. albus, S. venezuelae and S. avermitilis, as heterologous expression systems.

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Phage P1-Derived Artificial Chromosomes Facilitate Heterologous Expression of the FK506 Gene Cluster

Cited by 80 publications

References 52 publications

New Cyclodepsipeptide Derivatives Revealed by Genome Mining and Molecular Networking

New Cyclodepsipeptide Derivatives Revealed by Genome Mining and Molecular Networking

High‐Performance Polymers from Nature: Catalytic Routes and Processes for Industry

Streptomycetes: Surrogate hosts for the genetic manipulation of biosynthetic gene clusters and production of natural products

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