Microbial synthesis of medium-chain chemicals from renewables

Sarria, Stephen; Kruyer, Nicholas S; Peralta‐Yahya, Pamela

doi:10.1038/nbt.4022

Cited by 122 publications

(77 citation statements)

References 79 publications

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“…One approach that shows potential for the biological production of chemicals from renewable resources, the carboxylate platform (1, 2), uses anaerobic microbial communities to biotransform complex substrates into carboxylic acids, including medium-chain fatty acids (MCFA). MCFA such as hexanoate (a six carbon monocarboxylate, C6) and octanoate (an eight carbon monocarboxylate, C8) are used in large quantities for the production of pharmaceuticals, antimicrobials, and industrial materials, and can be processed to chemicals currently derived from fossil fuels (3, 4).…”

Section: Introductionmentioning

confidence: 99%

Metatranscriptomic and thermodynamic insights into medium-chain fatty acid production using an anaerobic microbiome

Scarborough

Lawson

Hamilton

et al. 2018

Preprint

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Importance 46Mixed communities of microbes play important roles in health, the environment, 47 agriculture, and biotechnology. While tapping the combined activity of organisms within 48 microbiomes may have advantages over the use of pure cultures for biomanufacturing, 49 harnessing the metabolism of these mixed cultures remains a major challenge. Here, we 50 predict metabolic functions of bacteria in a microbiome that produces medium-chain fatty 51 acids from a renewable feedstock. Our approach and findings can be used to engineer and 52 control microbiomes for improved biomanufacturing; to build synthetic mixtures of 53 microbes that produce valuable chemicals from renewable resources; and to better 54 understand microbial communities that contribute to health, agriculture, and the 55 environment. 56 microorganisms (1). In addition, MCFA producing bioreactors contain diverse communities 80 with members affiliated with the Firmicutes, particularly Clostridia and Lactobacilli, having 81 high abundance (4, 5, 11). However, the specific roles of the abundant microbiome 82 members are not well understood. 83Here, we utilize a combination of metagenomic, metatranscriptomic , pathway 84 modeling, and thermodynamic analyses to reconstruct the combined metabolic activity of a 85 microbiome converting lignocellulosic conversion residues to C6 and C8. In total, 37 high 86 quality draft metagenome-assembled genomes (MAGs) were assembled, and the gene 87 expression patterns of those representing the ten most abundant community members 88 during steady-state reactor operation were analyzed. Our results identify several MAGs in 89 the community that expressed genes predicted to be involved in complex carbohydrate 90 degradation and in the subsequent fermentation of degradation products to lactate and 91 acetate. Genes encoding enzymes capable of producing C6 and C8 from these fermentation 92 products were expressed by two abundant MAGs affiliated with the class Clostridia. Based 93 on a thermodynamic analysis of the proposed MCFA-producing pathways, we predict that 94 individual Clostridial MAGs use different substrates for MCFA production (lactate, versus a 95 combination of xylose, H2, and acetate). We also describe how new insights into MCFA 96 production could improve the biomanufacturing productivity of microbiomes. 97 Results 98 Microbiome characterization 99We previously described the establishment of a microbiome that produces MCFA in 100 a bioreactor that is continuously fed with the residues from lignocellulosic ethanol 101 production (4). The reactor feed contained high amounts of xylose, carbohydrate 102 6 oligomers, and uncharacterized organic matter (Fig. 1). Following an initial acclimation 103 period (Day 0 -Day 48), the quantity of produced organic acids stabilized (Fig. 1). To gain 104 insight into the microbial activities that were associated with this MCFA-producing 105 microbiome, samples were collected for metagenomic analysis at five different times (Days 106 12, 48, 84, 96, and 120), and RNA was pre...

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Section: Introductionmentioning

confidence: 99%

Metatranscriptomic and thermodynamic insights into medium-chain fatty acid production using an anaerobic microbiome

Scarborough

Lawson

Hamilton

et al. 2018

Preprint

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“…Typical examples of this sort of manipulations include manipulations leading to increased pyruvate or acetyl-coenzyme A (CoA) levels. These central metabolites can be used as building blocks in recombinant E. coli for small molecules such as butanol (Shen et al, 2011), or more complex chemical species such as polyhydroxyalkanoates [PHAs (Anjum et al, 2016;Chen and Jiang, 2017), specially the simplest form of these polymers, poly(3-hydroxybutyrate), PHB (Gomez et al, 2012)] and fatty acids (Sarria et al, 2017). The strategies used for enhancing the formation of such metabolic precursors usually involve deleting reactions that deplete pyruvate or acetyl-CoA or boosting carbon fluxes through glycolytic pathways (S anchez-Pascuala et al, 2017).…”

Section: Escherichia Colimentioning

confidence: 99%

Chasing bacterial chassis for metabolic engineering: a perspective review from classical to non‐traditional microorganisms

Calero

Nikel

2018

Microbial Biotechnology

207

173

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The last few years have witnessed an unprecedented increase in the number of novel bacterial species that hold potential to be used for metabolic engineering. Historically, however, only a handful of bacteria have attained the acceptance and widespread use that are needed to fulfil the needs of industrial bioproduction - and only for the synthesis of very few, structurally simple compounds. One of the reasons for this unfortunate circumstance has been the dearth of tools for targeted genome engineering of bacterial chassis, and, nowadays, synthetic biology is significantly helping to bridge such knowledge gap. Against this background, in this review, we discuss the state of the art in the rational design and construction of robust bacterial chassis for metabolic engineering, presenting key examples of bacterial species that have secured a place in industrial bioproduction. The emergence of novel bacterial chassis is also considered at the light of the unique properties of their physiology and metabolism, and the practical applications in which they are expected to outperform other microbial platforms. Emerging opportunities, essential strategies to enable successful development of industrial phenotypes, and major challenges in the field of bacterial chassis development are also discussed, outlining the solutions that contemporary synthetic biology-guided metabolic engineering offers to tackle these issues.

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“…This bioprocess relies on the combined metabolism of an anaerobic microbiome to hydrolyze complex organic substrates, ferment the hydrolyzed products to small organic intermediates (2 to 3 carbon molecules), and elongate these fermentation products to medium-chain fatty acids (MCFA; 6 to 8 carbon molecules) through reverse β-oxidation (1). MCFA are an attractive product due to their high value, relatively low solubility in water, and potential to offset fossil fuel demands for petrochemicals and other products (2, 3). Bioreactors performing chain elongation also provide model systems for studying the metabolic contributions of uncultured organisms to this process.…”

Section: Introductionmentioning

confidence: 99%

Multi-omic analysis of medium-chain fatty acid synthesis byCandidatusWeimerbacter bifidus, gen. nov., sp. nov., andCandidatusPseudoramibacter fermentans, sp. nov.

Scarborough

Myers

Donohue

et al. 2019

Preprint

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Chain elongation is emerging as a bioprocess to produce valuable medium-chain fatty acids (MCFA; 6 to 8 carbons in length) from organic waste streams by harnessing the metabolism of anaerobic microbiomes. Although our understanding of chain elongation physiology is still evolving, the reverse β-oxidation pathway has been identified as a key metabolic function to elongate the intermediate products of fermentation to MCFA. Here, we describe two chain-elongating microorganisms that were enriched in an anaerobic microbiome transforming the residues from a lignocellulosic biorefining process to short- and medium-chain fatty acids. Based on a multi-omic analysis of this microbiome, we predict that Candidatus Weimerbacter bifidus, gen. nov., sp. nov. used xylose to produce MCFA, whereas Candidatus Pseudoramibacter fermentans, sp. nov., used glycerol and lactate as substrates for chain elongation. Both organisms are predicted to use an energy conserving hydrogenase to improve the overall bioenergetics of MCFA production.IMPORTANCEMicrobiomes are vital to human health, agriculture, environmental processes, and are receiving attention as biological catalysts for production of renewable industrial chemicals. Chain elongation by MCFA-producing microbiomes offer an opportunity to produce valuable chemicals from organic streams that otherwise would be considered waste. However, the physiology and energetics of chain elongation is only beginning to be studied, and we are analyzing MCFA production by self-assembled communities to complement the knowledge that has been acquired from pure culture studies. Through a multi-omic analysis of an MCFA-producing microbiome, we characterized metabolic functions of two chain elongating bacteria and predict previously unreported features of this process.

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Microbial synthesis of medium-chain chemicals from renewables

Cited by 122 publications

References 79 publications

Metatranscriptomic and thermodynamic insights into medium-chain fatty acid production using an anaerobic microbiome

Metatranscriptomic and thermodynamic insights into medium-chain fatty acid production using an anaerobic microbiome

Chasing bacterial chassis for metabolic engineering: a perspective review from classical to non‐traditional microorganisms

Multi-omic analysis of medium-chain fatty acid synthesis byCandidatusWeimerbacter bifidus, gen. nov., sp. nov., andCandidatusPseudoramibacter fermentans, sp. nov.

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