Heterologous expression of bacterial natural product biosynthetic pathways

Huo, Liujie; Hug, Joachim J.; Fu, Chengzhang; Bian, Xiaoying; Zhang, Youming; Müller, Rolf

doi:10.1039/c8np00091c

Cited by 189 publications

(133 citation statements)

References 210 publications

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“…29 Bacterial NRPs have been mainly examined in bacterial systems and are typically smallscale batch-mode proof-of-concept studies, conducted in the model bacterium Escherichia coli, 65,66 or hosts that natively express NRPSs such as Streptomyces sp. 67 Most recently, a study in S. cerevisiae used the bpsA based indigoidine production to examine the impact of carbon catabolite repression on the production of heterologous TCA cycle derived products. 29 However, as a Crabtree-positive yeast that cannot efficiently utilize the major classes of carbon present in lignocellulosic biomass, S. cerevisiae may not be an ideal system for the sustainable production of this NRP.…”

Section: Fed-batch Process With Ph Control Results In Increase Of Indmentioning

confidence: 99%

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

et al. 2019

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Section: Fed-batch Process With Ph Control Results In Increase Of Indmentioning

confidence: 99%

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

et al. 2019

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“…It has been revealed that fungi possess far more gene clusters encoding secondary metabolites than their characterized compounds (Khaldi et al, 2010). In order to solve this challenge, a number of manipulations have been used to regulate the production of secondary metabolites from fungi, such as One strain many compounds (OSMAC) (Pan et al, 2019), co-culture (Yu et al, 2019), interspecies crosstalk (Wang et al, 2019), and heterologous expression (Huo et al, 2019;Zhang et al, 2019). Among these methods, chemical epigenetic manipulation has been demonstrated to be a promising strategy to wake the silent biosynthetic gene clusters to obtain novel compounds and has been applied to the marine fungi (Asai et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Terpenoids From the Coral-Derived Fungus Trichoderma harzianum (XS-20090075) Induced by Chemical Epigenetic Manipulation

et al. 2020

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The soft coral-derived fungus Trichoderma harzianum (XS-20090075) was found to be a potential strain to produce substantial new compounds in our previous study. In order to explore its potential to produce more metabolites, chemical epigenetic manipulation was used on this fungus to wake its sleeping genes, leading to the significant changes of its secondary metabolites by using a histone deacetylase (HDAC) inhibitor. The most obvious difference was the original main products harziane diterpenoids were changed into cyclonerane sesquiterpenoids. Three new terpenoids were isolated from the fungal culture treated with 10 µM sodium butyrate, including cleistanthane diterpenoid, harzianolic acid A (1), harziane diterpenoid, harzianone E (2), and cyclonerane sesquiterpenoid, 3,7,11-trihydroxy-cycloneran (3), together with 11 known sesquiterpenoids (4-14). The absolute configurations of 1-3 were determined by single-crystal X-ray diffraction, ECD and OR calculations, and biogenetic considerations. This was the first time to obtain cleistanthane diterpenoid and africane sesquiterpenoid from genus Trichoderma, and this was the first chlorinated cleistanthane diterpenoid. These results demonstrated that the chemical epigenetic manipulation should be an efficient technique for the discovery of new secondary metabolites from marinederived fungi.

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“…However, while the “orphan clusters” become available by the advent of next generation sequencing technologies and bioinformatics tools, the substances can often neither be identified nor extracted under laboratory conditions. Cultivation of the native producer strain in the laboratory is of limited success, because the native conditions cannot be reconstituted in the lab 3 , and robust heterologous production of the compound in host organisms fails owing to complex native regulation and possible toxic products 4-5 . Concomitantly, the proteins encoded by gene clusters escape enzymatic characterization, catalytic mechanisms remain unsolved and protein engineering for expanding the product spectra to novel new-to-nature compounds remains unachievable.…”

Section: Introductionmentioning

confidence: 99%

Cell-free synthesis of natural compounds from genomic DNA of biosynthetic gene clusters

Siebels

Nowak

Heil

et al. 2020

Preprint

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18A variety of chemicals can be produced in a living host cell via optimized and engineered 19 biosynthetic pathways. Despite the successes, pathway engineering remains demanding 20 and partly impossible owing to the lack of specific functions or substrates in the host 21 cell, its sensitivity in vital physiological processes to the heterologous components, or 22 constrained mass transfer across the membrane. In this study, we demonstrate that cell-23 free systems can be useful in driving the characterization and engineering of 24 biosynthetic pathways. We show that complex multidomain proteins involved in natural 25 compound biosynthesis can be produced from encoding DNA in vitro in a minimal 26 complex PURE system to directly run multistep reactions. We prove the concept of this 27 approach on the direct synthesis of indigoidine and rhabdopeptides with the in vitro 28 produced multidomain megasynthases BpsA and KJ12ABC. The in vitro produced 29 proteins are analyzed in detail, i.e., in yield, quality, post-translational modification and 30 specific activity, and compared to recombinantly produced proteins. Our study 31 highlights cell-free PURE systems as suitable setting for the rapid engineering of 32 biosynthetic pathways. 33 34 Keywords: cell-free protein synthesis, PURE system, natural products, biosynthetic 35 pathways, non-ribosomal peptide synthetase, polyketide synthase

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Heterologous expression of bacterial natural product biosynthetic pathways

Abstract: The review highlights the 2013–2018 literature on the heterologous expression of bacterial natural product biosynthetic pathways and emphasises new techniques, heterologous hosts, and novel chemistry.

Cited by 189 publications

References 210 publications

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

Terpenoids From the Coral-Derived Fungus Trichoderma harzianum (XS-20090075) Induced by Chemical Epigenetic Manipulation

Cell-free synthesis of natural compounds from genomic DNA of biosynthetic gene clusters

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