A field of dreams: Lignin valorization into chemicals, materials, fuels, and health-care products

Biotechnology Advances, Journal Year: 2019, Volume and Issue: 37(6), P. 107360 - 107360

Published: April 6, 2019

Lignin is one of the most abundant renewable resources on earth and readily produced as a sidestream during biomass fractioning. So far, these large quantities lignin have been severely underutilized, thereby wasting this valuable renewable. Recent technological advances in recovery, breakdown, conversion now started forming first sustainable value chains to take advantage lignin. Microbial cell factories, inspired by nature's miscellaneous set lignin-degrading microbes, are at heart novel processes. success stories which enzymes pathways microbes were harnessed for biobased production from hold great promise upgrading polymer into value-added compounds.

Language: Английский

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Mixed plastics waste valorization through tandem chemical oxidation and biological funneling

Science, Journal Year: 2022, Volume and Issue: 378(6616), P. 207 - 211

Published: Oct. 13, 2022

Mixed plastics waste represents an abundant and largely untapped feedstock for the production of valuable products. The chemical diversity complexity these materials, however, present major barriers to realizing this opportunity. In work, we show that metal-catalyzed autoxidation depolymerizes comingled polymers into a mixture oxygenated small molecules are advantaged substrates biological conversion. We engineer robust soil bacterium, Pseudomonas putida, funnel compounds single exemplary product, either β-ketoadipate or polyhydroxyalkanoates. This hybrid process establishes strategy selective conversion mixed useful

Language: Английский

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

Microbial Biotechnology, Journal Year: 2018, Volume and Issue: 12(1), P. 98 - 124

Published: June 21, 2018

Summary 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 bacteria attained acceptance and widespread use are needed fulfil needs industrial bioproduction – synthesis very few, structurally simple compounds. One reasons this unfortunate circumstance has been dearth tools targeted genome engineering chassis , and, nowadays, synthetic biology is significantly helping bridge such knowledge gap. Against background, review, we discuss state art rational design construction robust engineering, presenting key examples secured place bioproduction. emergence also considered at light unique properties their physiology metabolism, practical applications which they expected outperform other microbial platforms. Emerging opportunities, essential strategies enable successful development phenotypes, major challenges field discussed, outlining solutions contemporary biology‐guided offers tackle these issues.

Language: Английский

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CRISPR RNA-guided integrases for high-efficiency, multiplexed bacterial genome engineering

Nature Biotechnology, Journal Year: 2020, Volume and Issue: 39(4), P. 480 - 489

Published: Nov. 23, 2020

Language: Английский

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Heterologous expression of bacterial natural product biosynthetic pathways

Natural Product Reports, Journal Year: 2019, Volume and Issue: 36(10), P. 1412 - 1436

Published: Jan. 1, 2019

Covering: 2013 to June 2018 Heterologous expression of natural product biosynthetic pathways is increasing interest in microbial biotechnology, drug discovery and optimization. It empowers not only the robust production valuable biomolecules more amenable heterologous hosts but also permits generation novel analogs through engineering. This strategy facilitates bioactive compounds following functional cryptic gene clusters (BGCs) from fastidious original producers or metagenomic DNA surrogate hosts, thus facilitating genome mining post-genomic era. review discusses recent advances trends pertaining bacterial products, with an emphasis on new techniques, chemistry since 2013.

Language: Английский

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Engineering Robust Production Microbes for Large-Scale Cultivation

Trends in Microbiology, Journal Year: 2019, Volume and Issue: 27(6), P. 524 - 537

Published: Feb. 25, 2019

Strain engineering in the laboratory often does not consider process requirements larger-scale bioreactors. Systems and synthetic biology can be applied to design microbial strains that allow reliable robust production on a large scale. Commercial platforms should selected developed based their relevance final goals. are increasingly used examine modulate complex biological systems. As such, many issues arising during scaling-up processes addressed using these approaches. We review differences between laboratory-scale cultures provide perspective those strain characteristics especially important scaling. has been range of systems for response bioreactors fluctuations nutrients, dissolved gases, other stresses. Synthetic both assess response, engineer improve production. discuss approaches tools context use microbes applications large-scale It is well recognized produce vast compounds, from fuels commodity chemicals pharmaceuticals fine [1Zhang M.M. et al.Engineering hosts bacterial natural products.Nat. Prod. Rep. 2016; 33: 963-987Crossref PubMed Google Scholar, 2Carbonell P. al.An automated design-build-test-learn pipeline enhanced chemicals.Commun. Biol. 2018; 1: 66Crossref Scopus (114) 3Beller H.R. al.Natural products as biofuels bio-based chemicals: fatty acids isoprenoids.Nat. 2015; 32: 1508-1526Crossref Scholar]. Correspondingly, efforts broaden scope demonstrate proof-of-concept pathways new molecules gaining number [2Carbonell 4Casini A. al.A pressure test make 10 90 days: external evaluation methods biology.J. Am. Chem. Soc. 140: 4302-4316Crossref (88) 5Campodonico M.A. al.Generation an atlas chemical Escherichia coli novel pathway prediction algorithm, GEM-Path.Metab. Eng. 2014; 25: 140-158Crossref (124) However, despite development convert nearly any carbon source into desired product, rather modest cases have seen successful transition industrial-scale marketed products. Economic competitiveness with established or biosynthetic routes factor. Low titers yields setting also need overcome proceed scale-up. at level core bioconversion technology, dominant cause this dearth implementation challenge associated predicting performance The environment commercial-scale bioreactor drastically different such shake flasks. long most do perform same way two scenarios [6Humphrey Shake flask fermentor: what we learned?.Biotechnol Progress. 1998; 14: 3-7Crossref (118) Thus, industrial scale-up necessarily goes beyond [7Willrodt C. al.Guiding efficient synthesis non-natural by physicochemical properties reactants.Curr. Opin. Biotechnol. 35: 52-62Crossref (23) 8Chubukov V. al.Synthetic chemicals.NPJ Applicat. 2: 16009Crossref (152) A recent places cost large-volume $100 million $1 billion USD [9Crater J.S. Lievense J.C. Scale-up processes.FEMS Microbiol. Lett. 365 (fny138)Crossref (98) risk failure high, de-risking chassis itself aspect engineering. Process practices system fairly established, multiple reviews written topic [10Junker B.H. methodologies yeast fermentation processes.J. Biosci. Bioeng. 2004; 97: 347-364Crossref (173) 11Young T.B. Fermentation scaleup: experience total environmental approach.Ann. N. Y. Acad. Sci. 1979; 326: 165-180Crossref (9) 12Schmidt F.R. Optimization scale up processes.Appl. 2005; 68: 425-435Crossref (221) In contrast, phenotype fluctuating conditions, genotypic drift long-term cultivation, physiological factors less explored, potential impacts only recently [8Chubukov 13Rugbjerg al.Diverse genetic error modes constrain production.Nat. Commun. 9: 787Crossref best area scale-down models, where numbers generated tested under conditions representative growth production, allowing better selection will more predictably [14Neubauer Junne S. Scale-down simulators metabolic analysis bioprocesses.Curr. 2010; 21: 114-121Crossref (138) 15Baez al.Simulation CO(2) gradients system: transcriptional study recombinant coli.Biotechnol. J. 2011; 6: 959-967Crossref (20) 16Caspeta L. al.The effect heating rate metabolism, stress, temperature-induced protein: study.Biotechnol. Bioengineer. 2009; 102: 468-482Crossref (60) 17de Jonge L.P. al.Scale-down penicillin Penicillium chrysogenum.Biotechnol. 944-958Crossref (71) 18Lara A.R. al.Living heterogeneities bioreactors: understanding effects cells.Mol. 2006; 34: 355-381Crossref (281) it remains difficult develop maintain when scaled up. Advances 19Lee S.Y. Kim H.U. strategies developing strains.Nat. 1061-1072Crossref (332) Scholar] may able solutions space. Beyond improvements without plasmids inducer requirement, there some ambitious questions posed. Can create genetically phenotypically stable prevent phenotypic subculturing seed cultures? reliably increase duration phase profitability process? track subpopulations causal parameters heterogeneity within culture? dynamically regulate genes respond inhibitory byproducts stresses reduce negative selections enhance performance? There examples studies address individually which, presented collectively, reveal full approach. Most ambitiously, envision predict how behave enable us pre-emptively meet needs (Figure 1). review, focus changes ways mitigate control responses. Though yet underutilized, excellent illustrate predictive engineered strains. wide chemical, physical, negatively impact product formation bioprocess microtiter plates, flasks, bench-scale bioreactors, ultimately commercial Compounding issue fact mimicking environments encountered stages high-throughput screening initial straightforward. Moreover, challenges vary host cultivation Furthermore, measurements performed plates flasks analyses conducted 2). This exacerbates optimization resolve subsequently bioprocesses toward commercialization. One conspicuous difference operating pressure. volumes increase, height water column creates increasing hydrostatic gradient. principle, influence properties, including enzyme activity cell membrane permeability viability flux [18Lara increased bottom raises concentration gases. For instance, CO2 (dCO2) equilibrium bicarbonate carbonate ions which contribute medium osmolarity affect broth pH. dCO2 could result accumulation gas itself, osmotic changes, pH even combination all three [20Zanghi J.A. al.Bicarbonate osmolality key determinants inhibition CHO polysialylation elevated pCO(2) pH.Biotechnol. 1999; 65: 182-191Crossref Other colloidal thermodynamic bulk viscosity, emulsion stability, biomass settling, influenced pressure, among factors. Adverse persist harvest efficiency quality downstream (e.g., solid–liquid separation, chromatography, extraction, crystallization, distillation, upgrading, polymerization), resulting higher costs reduced [21Kumar D. Murthy G.S. Impact pretreatment processing technologies economics energy cellulosic ethanol production.Biotechnol. Biofuels. 4: 27Crossref (250) With volume, mixing time increases few seconds (laboratory-scale) several minutes (hundreds cubic meters) internal components, spargers, baffles, cooling coils, dead zones poor mixing, heat transfer, gas–liquid mass transfer. imperfect results microenvironments inhomogeneities, pH, temperature, oxygen (DO), dCO2, nutrients. Combined, variations lead transient permanent insults oxidative damage, nutrient limitations, stress responses viability, productivity [22Deparis Q. tolerance industrially relevant factories.FEMS Yeast Res. 2017; 17 (fox036)Crossref (108) Additional cultivations arise raw material contaminants. To costs, utilize crude materials utilized little no refinement thus introduce impurities accumulate inhibitory/toxic levels. Some real-world feedstocks include corn slurry, steep liquor, sugar cane juice, molasses, beet agricultural residues, food-processing waste, municipal solid waste Microbial contamination materials, harsh further levels deleterious titer yield (TRY) metrics 23Serate al.Controlling hydrolysis AFEX-pretreated stover switchgrass: hydrolysate composition, fermentation.Biotechnol. 8: 180Crossref (33) 24Fischer C.R. al.Selection production.Metab. Engineer. 2008; 10: 295-304Crossref (305) 25Mohamed E.T. platform ionic liquid adaptive evolution.Microb. Cell Factor. 16: 204Crossref (48) 26Mukhopadhyay Tolerance bacteria advanced chemicals.Trends 23: 498-508Abstract Full Text PDF (160) These strain-screening assays, but priority underappreciated sensitivities understudied early strain/cultivation program sterile technique very pure commonly small-scale optimization. If account risks them outset, scaling would become predictable, case platforms. Exposure heterogeneous fermenters trigger 27Enfors S.O. al.Physiological bioreactors.J. 2001; 85: 175-185Crossref (348) 28Takors R. processes: impacts, open questions.J. 2012; 160: 3-9Crossref (126) High-throughput analytics, DNA sequencing −omics (fluxomics, transcriptomics, proteomics, metabolomics), platforms, characterized simulating scaled-down experiments. Mathematical models guidance designing forecasting learnings environment. approach probability metrics, TRY, translate fully quickly manufacturing plant, thereby minimizing start-up 29Delvigne F. al.Bioprocess scale-up/down integrative enabling technology: fluid mechanics beyond.Microb. 1267-1274Crossref (40) Heterogeneity substrates nutrient, inherent population examined context. Gas O2, parameter measurable bioreactor. grown batch resulted slower by-product [30Castan al.Oxygen enriched air supply human hormone.Enzyme Microb. Technol. 2002; 30: 847-854Crossref (42) Another found needed E. green fluorescent protein (GFP), observe glutamate decarboxylase α‐ketoglutarate dehydrogenase [15Baez comparative transcript revealed fast Corynebacterium glutamicum alternating levels, appeared strongly correlated strength pCO2 stimulus [31Buchholz al.CO₂/HCO₃⁻ perturbations simulated device glutamicum.Appl. 98: 8563-8572Crossref (38) authors observed expression encoding enzymes necessary oxaloacetate hypothesized rapid availability PEP/pyruvate carboxylation. first findings were reported Oosterhuis al. [32Oosterhuis N.M. gluconic acid Gluconobacter oxydans.Biotechnol. 1985; 27: 711-720Crossref (72) studies, oxydans was cycled low high More similar intracellular 33Lara al.Fast dynamic fermentative metabolism aerobic anaerobic glucose pulses.Biotechnol. 104: 1153-1161Crossref (57) 34Limberg M.H. al.Metabolic profile 1,5-diaminopentane producing conditions: blueprint robustness inhomogeneities.Biotechnol. 114: 560-575Crossref (36) 35Käß al.Assessment against oxygen/substrate oscillations DM1933 two-compartment bioreactor.Bioprocess Biosyst. 37: 1151-1162Crossref (37) 36von Wulffen al.Rapid sampling after changing reveals dynamics.Genes (Basel). 90Crossref (13) explained alterations stoichiometry kinetics, organic acids, indicating responds rapidly [33Lara Fu [37Fu Z. al.Exometabolome hypoxia up-scaling Saccharomyces cerevisiae high-cell density fed-batch biopharmaceutical process.Microb. Fact. 13: 32Crossref carried out exometabolome high-density scale, overflow metabolism. one Liu introduced VHb (Vitreoscilla hemoglobin, facilitating O2 transport) fatty-acid-producing promote yielded 70% compared its parental [38Liu al.Enhancing Vitreoscilla hemoglobin overexpression.Biotechnol. 463-467Crossref While (see Outstanding Questions), natively resilient [35Käß bottlenecks [39Wehrs M. al.Production non-ribosomal peptide indigoidine relies respiratory state cerevisiae.Microb. 17: 193Crossref evolution [40Sandberg T.E. al.Laboratory substrate distinct strategies.Appl. Environ. 83e00410-17Crossref (52) issue. Besides leading suboptimal transfer effects, impose cultures. Recent shown adopt short- withstand regarding [41Löffler – considering ATP expenses responses.Metab. 38: 73-85Crossref 42Löffler al.Switching nitrogen limitation: unraveling dynamics coli.J. 258: 2-12Crossref (12) 43Nieß al.Repetitive short-term stimuli imposed induce adaptation experimental evidence mathematical model.Front. 1195Crossref (19) 44Simen J.D. al.Transcriptional ammonia fluctuations.Microb. 858-872Crossref (27) chrysogenum, physiology investigated imposing intermittent feeding regime culture [17de that, while remained same, significantly intermittently fed observation reduction possibly caused AMP cerevisiae, genome-wide cross-regulation limitations (C,N,P,S) chemostat identified 155 oxygen-responsive responsive macronutritional [45Boer V.M. limited carbon, nitrogen, phosphorus, sulfur.J. 2003; 278: 3265-3274Crossref (264) 46Tai S.L. al.Two-dimensional transcriptome cultures: combinatorial macronutrient limitation cerevisiae.J. 280: 437-447Abstract (120) Data obtained mirroring cellular typical derive validate adequate silico predictions performance. optimize hardware configuration conditions. reductions TRY criteria improved manufacturing. Recently, metabolically structured kinetic model chrysogenum showed sufficient accuracy simulation timescales (which minutes) [47Tang W. 9-pool describing days 1733-1743Crossref (32) Nitrogen-responsive regulation another variation, C/N balance known output. relA, regulator responsible signal molecule guanosine tetraphosphate (ppGpp) stringent activated starvation major coupled manage [48Brown D.R. al.Nitrogen coli.Nat. 5: 4115Crossref (105) Michalowski combined mechanistic knowledge maintained constant ppGpp pool independently nutritional supply, pyruvate greater towards [49Michalowski al.Escherichia HGT: throughput slowly growing resting conditions.Metab. 40: 93-103Crossref (30) Stochasticity gene considered main population, due cell-to-cell variation promoter expression, unequal transporter distribution, bet-hedging diauxic shift [2

Language: Английский

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Microbial production of advanced biofuels

Nature Reviews Microbiology, Journal Year: 2021, Volume and Issue: 19(11), P. 701 - 715

Published: June 25, 2021

Language: Английский

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Industrial biotechnology of Pseudomonas putida: advances and prospects

Applied Microbiology and Biotechnology, Journal Year: 2020, Volume and Issue: 104(18), P. 7745 - 7766

Published: Aug. 13, 2020

Abstract Pseudomonas putida is a Gram-negative, rod-shaped bacterium that can be encountered in diverse ecological habitats. This ubiquity traced to its remarkably versatile metabolism, adapted withstand physicochemical stress, and the capacity thrive harsh environments. Owing these characteristics, there growing interest this microbe for industrial use, corresponding research has made rapid progress recent years. Hereby, strong drivers are exploitation of cheap renewable feedstocks waste streams produce value-added chemicals steady genetic strain engineering systems biology understanding bacterium. Here, we summarize advances prospects engineering, synthetic biology, applications P. as cell factory. Key points • global Novel tools enable system-wide streamlined genomic engineering. Applications range from bioeconomy biosynthetic drugs.

Language: Английский

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High‐quality genome‐scale metabolic modelling of Pseudomonas putida highlights its broad metabolic capabilities

Environmental Microbiology, Journal Year: 2019, Volume and Issue: 22(1), P. 255 - 269

Published: Oct. 28, 2019

Genome-scale reconstructions of metabolism are computational species-specific knowledge bases able to compute systemic metabolic properties. We present a comprehensive and validated reconstruction the biotechnologically relevant bacterium Pseudomonas putida KT2440 that greatly expands computable predictions its states. The represents significant reactome expansion over available reconstructed bacterial networks. Specifically, iJN1462 (i) incorporates several hundred additional genes associated reactions resulting in new predictive capabilities, including nutrients supporting growth; (ii) was by vivo growth screens included previously untested carbon (48) nitrogen (41) sources; (iii) yielded gene essentiality showing large accuracy when compared with knock-out library Bar-seq data; (iv) allowed mapping network 82 P. sequenced strains revealing functional core reflect versatility this species, aromatic compounds derived from lignin. Thus, study provides thoroughly updated phenotypes for putida, which can be leveraged as first step toward understanding pan capabilities Pseudomonas.

Language: Английский

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Lignocellulosic crop residue composting by cellulolytic nitrogen-fixing bacteria: A novel tool for environmental sustainability

The Science of The Total Environment, Journal Year: 2020, Volume and Issue: 715, P. 136912 - 136912

Published: Jan. 25, 2020

Language: Английский

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