Designer Microbial Ecosystems – Toward Biosynthesis with Engineered Microbial Consortia

Babson, David; Held, Mark; Schmidt‐Dannert, Claudia

doi:10.1002/9781118794623.ch2

Cited by 4 publications

(3 citation statements)

References 67 publications

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“…Alternative protein and small molecule payloads from a general autolytic delivery system could be designed to mediate microbial interactions, aid in bioprocessing or bioremediation or as a cellular therapeutic. Further, stochastic strategies could be employed with or without self-destructive altruism to seed multicellular developmental programs for distributed metabolic engineering 34 , evolutionary engineering 35 or to control distributions of multiple cell types in microbial communities 36,37 . Tunable developmental programs could also be applied to better understand the emergence and persistence of wellstudied developmental programs, substituting complex regulation with tunable differentiation dynamics.…”

Section: Is2mentioning

confidence: 99%

Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization

Egbert

Brettner

Zong

et al. 2016

Preprint

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Stochastic differentiation and programmed cell death are common developmental processes in microbes, driving diverse altruistic behaviors that promote cooperation. Utilizing cell death in developmental programs requires control over the rate of differentiation to balance cell proliferation against the utility of sacrifice. However, the regulatory networks that control these behaviors are often complex and have yet to be successfully harnessed as biotechnology. Here, we engineered a synthetic developmental gene network that couples stochastic differentiation with programmed cell death to implement a two-member division of labor. Progenitor cellobiose consumer cells were engineered to grow on cellobiose and differentiate at a controlled rate into self-destructive altruists that release an otherwise sequestered cellulase enzyme payload through autolysis to form a developmental Escherichia coli consortium that utilizes cellulose for growth. We used an experimentally parameterized model of task switching, payload delivery and cellulose conversion to nutrients to set key parameters to achieve overall population growth supported by cellulase release, liberating 14-23% of the available carbon. An inevitable consequence of engineering altruistic developmental behaviors is the emergence of cheaters that undermine cooperation. We observed cheater phenotypes for consumers and altruists, identified mutational hotspots and constructed a predictive model of circuit longeivity based on mutation rate estimates for each mode of evolutionary escape. This work introduces the altruistic developmental program as a new tool for synthetic biology, demonstrates the utility of population dynamics models to engineer complex phenotypes and provides a testbed for probing the evolutionary biology of selfdestructive altruism.

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Section: Is2mentioning

confidence: 99%

Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization

Egbert

Brettner

Zong

et al. 2016

Preprint

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“…There are several advantages of using nutritional and functional microorganisms: (1) Microbial production is an applicable and economical technology to obtain stable products and maintain the cell culture [ 56 , 57 ]. (2) It is eco-friendly because microorganisms that are considered as coproducts from the food industry or biofuel production could be recyclable and supplemented in animal diets [ 56 , 58 ]. (3) Microorganisms are high in nutrients, such as protein, AA, fats, and vitamins, and can be useful in animal diets.…”

Section: Introductionmentioning

confidence: 99%

Use of Microorganisms as Nutritional and Functional Feedstuffs for Nursery Pigs and Broilers

Cheng

Kim

2022

Animals

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The objectives of this review paper are to introduce the structures and composition of various microorganisms, to show some applications of single cells as alternative protein supplements or energy feeds in swine and poultry diets, and to discuss the functional effects of microorganisms as feed additives on the growth performance and intestinal health of nursery pigs and broilers. Microorganisms, including bacteria, yeasts, and microalgae, have been commonly supplemented in animal diets because they are cost-effective, stable, and have quantitative production that provides nutritional and functional benefits to pigs and broilers. Microorganisms could be alternative antibiotics to enhance intestinal health due to bioactive components from cell wall components, which interact with receptors on epithelial and immune cells. In addition, bioactive components could be digested by intestinal microbiota to produce short-chain fatty acids and enhance energy utilization. Otherwise, microorganisms such as single-cell protein (SCP) and single-cell oils (SCOs) are sustainable and economic choices to replace conventional protein supplements and energy feeds. Supplementing microorganisms as feedstuffs and feed additives improved the average daily gain by 1.83%, the daily feed intake by 0.24%, and the feed efficiency by 1.46% in pigs and broilers. Based on the properties of each microorganism, traditional protein supplements, energy feeds, and functional feed additives could be replaced by microorganisms, which have shown benefits to animal’s growth and health. Therefore, specific microorganisms could be promising alternatives as nutritional and functional feedstuffs in animal diets.

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“…With regard to certain aspects, synthetic microbial consortia offer many advantages over monocultures (Babson, Held, & Schmidt‐Dannert, 2014; Nakagawa et al, 2016). Artificial consortia, formed for example, of Trichoderma reesei and Escherichia coli (Minty et al, 2013), and those formed of cellulolytic Clostridia and solventogenic Clostridia (Nakayama, Kiyoshi, Kadokura, & Nakazato, 2011; Wang et al, 2015; Wen et al, 2014b; Yu, Chan, & Saddler, 1985) have been developed for the production of cellulosic butanol or isobutanol.…”

Section: Introductionmentioning

confidence: 99%

Combined evolutionary engineering and genetic manipulation improve low pH tolerance and butanol production in a synthetic microbial Clostridium community

Wen

Ledesma-Amaro

et al. 2020

Biotech & Bioengineering

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Synthetic microbial communities have become a focus of biotechnological research since they can overcome several of the limitations of single‐specie cultures. A paradigmatic example is Clostridium cellulovorans DSM 743B, which can decompose lignocellulose but cannot produce butanol. Clostridium beijerinckii NCIMB 8052 however, is unable to use lignocellulose but can produce high amounts of butanol from simple sugars. In our previous studies, both organisms were cocultured to produce butanol by consolidated bioprocessing. However, such consolidated bioprocessing implementation strongly depends on pH regulation. Since low pH (pH 4.5–5.5) is required for butanol fermentation, C. cellulovorans cannot grow well and saccharify sufficient lignocellulose to feed both strains at a pH below 6.4. To overcome this bottleneck, this study engineered C. cellulovorans by adaptive laboratory evolution, inactivating cell wall lyases genes (Clocel_0798 and Clocel_2169), and overexpressing agmatine deiminase genes (augA, encoded by Cbei_1922) from C. beijerinckii NCIMB 8052. The generated strain WZQ36: 743B*6.0*3△lyt0798△lyt2169‐(pXY1‐Pthl‐augA) can tolerate a pH of 5.5. Finally, the alcohol aldehyde dehydrogenase gene adhE1 from Clostridium acetobutylicum ATCC 824 was introduced into the strain to enable butanol production at low pH, in coordination with solvent fermentation of C. beijerinckii in consortium. The engineered consortium produced 3.94 g/L butanol without pH control within 83 hr, which is more than 5‐fold of the level achieved by wild consortia under the same conditions. This exploration represents a proof of concept on how to combine metabolic and evolutionary engineering to coordinate coculture of a synthetic microbial community.

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Designer Microbial Ecosystems – Toward Biosynthesis with Engineered Microbial Consortia

Cited by 4 publications

References 67 publications

Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization

Self-destructive altruism in a synthetic developmental program enables complex feedstock utilization

Use of Microorganisms as Nutritional and Functional Feedstuffs for Nursery Pigs and Broilers

Combined evolutionary engineering and genetic manipulation improve low pH tolerance and butanol production in a synthetic microbial Clostridium community

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