Circuit-guided population acclimation of a synthetic microbial consortium for improved biochemical production

Abstract

Microbial consortia have been considered potential platforms for bioprocessing applications. However, the complexity in process control owing to the use of multiple strains necessitates the use of an efficient population control strategy. Herein, we report circuit-guided synthetic acclimation as a strategy to improve biochemical production by a microbial consortium. We designed a consortium comprising alginate-utilizing Vibrio sp. dhg and 3-hydroxypropionic acid (3-HP)-producing Escherichia coli strains for the direct conversion of alginate to 3-HP. We introduced a genetic circuit, named “Population guider”, in the E. coli strain, which degrades ampicillin only when 3-HP is produced. In the presence of ampicillin as a selection pressure, the consortium was successfully acclimated for increased 3-HP production by 4.3-fold compared to that by a simple co-culturing consortium during a 48-h fermentation. We believe this concept is a useful strategy for the development of robust consortium-based bioprocesses.

A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast

“…In another example, a consortium for a cooperative relationship between alginate-utilizing Vibrio sp. dhg and 3-hydroxypropionic acid (3-HP)-producing Escherichia coli strains has been established, allowing the direct conversion of alginate to 3-HP 55 . For carbon-negative processing, pairwise SMC can be defined between C 1 -consuming autotrophic bacteria and yeast 56 .…”

Identifying LasR Quorum Sensors with Improved Signal Specificity by Mapping the Sequence–Function Landscape

“…The use of engineered bacterial consortia to distribute tasks among different strains has gained great interest in various applications, such as biomanufacturing, , bioremediation, , therapeutics, , and agriculture. , This strategy can offer reduced cellular burden of microbial members and the ability for specialization that leverages each microorganism’s traits. − For engineered bacterial consortia to function robustly, programmable cell–cell communication is required to coordinate processes in different cells and control their spatiotemporal dynamics, which has been achieved via diffusible chemical intercellular signaling, − cell–cell adhesion, , and conjugal transfer of DNA. − In nature, bacteria commonly communicate via diffusible quorum sensing signals to elicit population-level and cell density-dependent responses. − Various quorum sensing signals have been used as chemical signals in engineered microbial consortia, including oligopeptides, , γ-butyrolactone, and homoserine lactones. − Among these, homoserine lactones (HSLs) have been most widely utilized in synthetic biology due to the relative ease of signal production and sensing. − In these systems, the canonical LuxR-type allosteric transcription factor binds to its cognate HSL ligand, and after complexation, activates transcription from its corresponding quorum sensing promoter. , HSLs for LuxR-type regulators contain a lactone ring and commonly an acyl chain that can vary in length (4 to 20 carbons), degree of saturation, and oxidation state at the third carbon. , Structural similarity can cause noncognate HSL signals to activate LuxR-type quorum sensors resulting in signal crosstalk, − which can be problematic for precise control of functions in microbial consortia when using multiple quorum sensing systems.…”

Phylogeny-metabolism dual-directed single-cell genomics for dissecting and mining ecosystem function

“…Via their rich and diverse metabolic activities, microbial consortia have supported most if not all of the critical ecological processes on Earth, such as geochemical cycling of elements, environmental remediation and nutrient utilization in hosts ( 1-3 ). To dissect their functioning mechanisms, and also mine the underlying bioresources (e.g., useful chassis cells or enzymes), two major strategies are usually adopted.…”