Applied Microbiology and Biotechnology

, Volume 101, Issue 20, pp 7427–7434 | Cite as

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

  • Jeffrey Czajka
  • Qinhong Wang
  • Yechun WangEmail author
  • Yinjie J. TangEmail author


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.


Channeling Corynebacterium glutamicum Cyanobacteria Knowledge engineering Rhodococcus Yarrowia lipolytica 



This work is supported by two National Science Foundation grants (IIP 1722313 and MCB 1616619) and Industrial Biotechnology Program of Tianjin Municipal Science and Technology Commission (14ZCZDSY00066).

Compliance with ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Energy, Environmental and Chemical EngineeringWashington UniversitySaint LouisUSA
  2. 2.CAS Key Laboratory of Systems Microbial BiotechnologyTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS)TianjinChina
  3. 3.Arch Innotek, LLCSt LouisUSA

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