Synthetic biology for manufacturing chemicals: constraints drive the use of non-conventional microbial platforms.

Publisher: Springer International Country of Publication: Germany NLM ID: 8406612 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0614 (Electronic) Linking ISSN: 01757598 NLM ISO Abbreviation: Appl Microbiol Biotechnol Subsets: MEDLINE

Original Publication: Berlin ; New York : Springer International, c1984-

Biotechnology/*methods ; Corynebacterium glutamicum/*metabolism ; Cyanobacteria/*metabolism ; Industrial Microbiology/*methods ; Rhodococcus/*metabolism ; Synthetic Biology/*methods ; Yarrowia/*metabolism; Corynebacterium glutamicum/genetics ; Cyanobacteria/genetics ; Rhodococcus/genetics ; Yarrowia/genetics

Genetically modified microbes have had much industrial success producing protein-based products (such as antibodies and enzymes). However, engineering microbial workhorses for biomanufacturing of commodity compounds remains challenging. First, microbes cannot afford burdens with both overexpression of multiple enzymes and metabolite drainage for product synthesis. Second, synthetic circuits and introduced heterologous pathways are not yet as "robust and reliable" as native pathways due to hosts' innate regulations, especially under suboptimal fermentation conditions. Third, engineered enzymes may lack channeling capabilities for cascade-like transport of metabolites to overcome diffusion barriers or to avoid intermediate toxicity in the cytoplasmic environment. Fourth, moving engineered hosts from laboratory to industry is unreliable because genetic mutations and non-genetic cell-to-cell variations impair the large-scale fermentation outcomes. Therefore, synthetic biology strains often have unsatisfactory industrial performance (titer/yield/productivity). To overcome these problems, many different species are being explored for their metabolic strengths that can be leveraged to synthesize specific compounds. Here, we provide examples of non-conventional and genetically amenable species for industrial manufacturing, including the following: Corynebacterium glutamicum for its TCA cycle-derived biosynthesis, Yarrowia lipolytica for its biosynthesis of fatty acids and carotenoids, cyanobacteria for photosynthetic production from its sugar phosphate pathways, and Rhodococcus for its ability to biotransform recalcitrant feedstock. Finally, we discuss emerging technologies (e.g., genome-to-phenome mapping, single cell methods, and knowledge engineering) that may facilitate the development of novel cell factories.

MCB 1616619 Directorate for Biological Sciences; IIP 1722313 Directorate for Engineering; 14ZCZDSY00066 Industrial Biotechnology Program of Tianjin Municipal Science and Technology Commission

Keywords: Channeling; Corynebacterium glutamicum; Cyanobacteria; Knowledge engineering; Rhodococcus; Yarrowia lipolytica

Date Created: 20170909 Date Completed: 20180625 Latest Revision: 20180710

20250114

10.1007/s00253-017-8489-9

28884354