Host Organisms: Myxobacterium

Wenzel, Silke C.; Müller, Rolf

doi:10.1002/9783527807796.ch12

Cited by 3 publications

(5 citation statements)

References 143 publications

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Section: Results and Discussionmentioning

confidence: 99%

“…In order to establish a versatile production platform for argyrins we aimed at heterologous expression of the pathway in a well-established host for myxobacterial megasynthetases, Myxococcus xanthus. 33 We intended to generate BGC DNA fragments via gene synthesis, which allows for modulation of arg sequences according to requirements relevant for BGC assembly, engineering and heterologous expression (Figure 2). For arg BGC design, the native pathway from Cystobacter sp.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…As host strain we aimed to employ the myxobacterial model strain Myxococcus xanthus DK1622, which led to the most promising yields in previous expression studies with myxobacterial megasynthetases. 33 However, to simplify the production spectra and to probably cause additional beneficial effects on heterologous argyrin biosynthesis (e.g., reduce precursor competition) we first deleted the BGC that is in charge of lipopeptide production in the host (mch A BGC 52 ). The corresponding products, myxochromides A, represent one of the most abundant compound families produced in M. xanthus under standard cultivation conditions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Next we envisaged the establishment of a versatile microbial production platform to facilitate future exploitation of argyrins and novel derivatives thereof. As genetic engineering of the native argyrin producer strains is difficult we intended to heterologously express the arg BGC in a derivative of the myxobacterial model strain Myxococcus xanthus , which turned out to be a suitable host for expression of other natural product pathways from myxobacteria in the past . Synthetic biology approaches were applied to design and construct different synthetic versions of the argyrin BGC based on synthetic DNA and to engineer the argyrin production spectrum.…”

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confidence: 99%

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Biosynthesis and Heterologous Production of Argyrins

et al. 2019

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Argyrins represent a family of cyclic octapeptides exhibiting promising antimicrobial, antitumorigenic and immunosuppressant activities. They derive from a nonribosomal peptide synthetase pathway, which was identified and characterized in this study from the myxobacterial producer strain Cystobacter sp. SBCb004. Using the native biosynthetic gene cluster (BGC) sequence as template synthetic BGC versions were designed and assembled from gene synthesis fragments. A heterologous expression system was established after chromosomal deletion of a wellexpressed lipopeptide pathway from the host strain Myxococcus xanthus DK1622. Different approaches were applied to engineer and improve heterologous argyrin production, which was finally increased to 160 mg/L, around 20-fold higher yields compared to the native producer. Heterologous production platform also led to identification of several novel argyrin derivatives (A2, F3, G3, I, J, K, and L). The optimized production system provides a versatile platform for future supply of argyrins and novel derivatives thereof.

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Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

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confidence: 99%

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Biosynthesis and Heterologous Production of Argyrins

et al. 2019

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“…93,99 M. xanthus is currently the best choice for the expression of myxobacterial BGCs, especially for polyketide BGCs. 100 Bacillus subtilis has generally been used for heterologous expression of rmicute or actinomyces BGCs. 101 Pseudomonas putida is also a versatile host for the production of natural products, such as myxobacterial myxochromide S and pretubulysin.…”

Section: Emerging Heterologous Hosts For Natural Product Productionmentioning

confidence: 99%

Heterologous expression of bacterial natural product biosynthetic pathways

et al. 2019

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Correlating chemical diversity with taxonomic distance for discovery of natural products in myxobacteria

et al. 2018

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Some bacterial clades are important sources of novel bioactive natural products. Estimating the magnitude of chemical diversity available from such a resource is complicated by issues including cultivability, isolation bias and limited analytical data sets. Here we perform a systematic metabolite survey of ~2300 bacterial strains of the order Myxococcales, a well-established source of natural products, using mass spectrometry. Our analysis encompasses both known and previously unidentified metabolites detected under laboratory cultivation conditions, thereby enabling large-scale comparison of production profiles in relation to myxobacterial taxonomy. We find a correlation between taxonomic distance and the production of distinct secondary metabolite families, further supporting the idea that the chances of discovering novel metabolites are greater by examining strains from new genera rather than additional representatives within the same genus. In addition, we report the discovery and structure elucidation of rowithocin, a myxobacterial secondary metabolite featuring an uncommon phosphorylated polyketide scaffold.

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Host Organisms: Myxobacterium

Cited by 3 publications

References 143 publications

Biosynthesis and Heterologous Production of Argyrins

Biosynthesis and Heterologous Production of Argyrins

Heterologous expression of bacterial natural product biosynthetic pathways

Correlating chemical diversity with taxonomic distance for discovery of natural products in myxobacteria

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