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  • Commentary
  • Open Access

New challenges and opportunities for industrial biotechnology

Microbial Cell Factories201211:111

  • Received: 13 August 2012
  • Accepted: 14 August 2012
  • Published:


Industrial biotechnology has not developed as fast as expected due to some challenges including the emergences of alternative energy sources, especially shale gas, natural gas hydrate (or gas hydrate) and sand oil et al. The weaknesses of microbial or enzymatic processes compared with the chemical processing also make industrial biotech products less competitive with the chemical ones. However, many opportunities are still there if industrial biotech processes can be as similar as the chemical ones. Taking advantages of the molecular biology and synthetic biology methods as well as changing process patterns, we can develop bioprocesses as competitive as chemical ones, these including the minimized cells, open and continuous fermentation processes et al.


  • Industrial biotechnology
  • Shale gas
  • Oil fields
  • PHB
  • Bioplastics
  • Biofuels
  • Bulk chemicals
The commercialization of industrial biotechnology is not as fast as we expected. Originally, we believe that production of bulk chemicals including biofuels, polymeric materials and chemical agents using microorganisms or enzymes will provide low cost, environmentally friendly products to partially replace petro-chemicals products[1]. However, this looks not so easy to materialize due to the facts that:
  1. 1.

    Petroleum does not rise in price too much after 2008 financial crisis, other alternative energy sources, especially shale gas, natural gas hydrate (or gas hydrate) and sand oil, have been discovered in large amount and their exploitations are increasingly moving toward a very competitive price;

  2. 2.

    The exhaustion of petroleum seems to be a remote reality

  3. 3.

    Agriculture raw materials for bioprocessing are becoming increasingly costly

  4. 4.

    Low cost raw material cellulose can not be easily used for microbial processes at least for the next 5–10 years

  5. 5.

    Bioprocessing is still not as effective as chemical processing, resulting in high cost of bio-products (Table1)

  6. 6.

    Bioprocessing that requires large amount of fresh water has had increasing concerns in many water shortage areas

  7. 7.

    The chemical industry is also evolving competitive in various ways including environmentally friendliness, the use of renewable resources (biomass) for making chemicals that are normally derived from petro-chemicals

  8. 8.

    The rapid development of C1 chemical engineering products

  9. 9.

    Large amount of funding is not more directed to industrial biotechnology.

Table 1

Comparison of industrial biotechnology and chemical technology


Industrial biotechnology

Chemical technology

Reaction Time

Slow: production takes days

Fast: production takes hours


Agricultural products

Petroleum or its derivatives

Conversion of substrates to products

Low: e.g. PHB/glucose ≈ 33 wt% PHA/fatty acids ≈ 60 wt%

High: e.g. Polyethylene/ethylene ≈ 100%



Mostly organic solvents

Consumption of water

A lot


Reaction conditions

30-40°C, normal pressure

Generally >100°C, High Pressures

Product concentration

Low: Several mg to 100 g/L

Very high

Product recovery cost

Very high

Low to medium


Normally discontinuous one

Can be continuous



No need

Production facility cost

Very high

Low to high (explosive proof)

Waste water

Not toxic, easier to treat

Generally toxic, difficult to treat

Taking the example of polyhydroxyalkanoates (PHA), a biopolyester family that has been exploited to become an industrial value chain[24], PHA has not been able to commercially produce in large scale due to the difficulty to lower the production cost especially for their applications as bioplastics that are considered as biodegradable and bio-based despite the possibility of using CO2 as substrate[5].

To successfully commercialize PHA, we must keep working hard on the “high volume and low price” strategy by developing better PHA production strains and cost competitive processes. While for some special applications, “low volumes and high price” can be applied, such as products to be used for biomedical purposes, specialty polymers[6, 7], chiral monomers, drug development and special applications et al.[8, 9]. And this is generally true in order to survive this competitive environment for industrial biotechnology, it must be competitive with the chemical industry. Let’s see what we can do to make this happen. In addition, it is also important to be able to develop processes that combined the advantages of chemical industry to supplement the weaknesses of industrial biotechnology (Table1).

The newly emerging synthetic biology approaches may offer some clues for developing competitive technology for industrial biotechnology to produce “high volume and low price” products (Table2). At the same time, bio-processing should try to become as similar as the chemical industry, including the need to develop continuous and open fermentation processes for e.g. making biofuels and PHA bioplastics[1012]. Also, from now and toward a distant future, foods are still important for feeding the world population, the development of bioprocesses based on kitchen waste or activated sludge as substrates may also be an important option for a competitive industrial biotechnology (Table2).
Table 2

Problems to be solved for making industrial biotechnology competitive to chemical technology


Weakness of Industrial biotechnology

Possible solutions

Microorganisms grow too slow

Slow: production takes days

Minimizing the microbial cells

Microbes can not use mixed substrates

Agricultural products are mostly mixed substrates

Assembling pathways that can metabolize mixed substrates

Low conversion of substrates to products

Cell metabolism turn substrates into CO2, H2O & byproducts

Removing unnecessary pathways consuming substrates

High Consumption on fresh H2O

Fresh H2O as medium et al.

Utilization of sea water for cell growth

Microbial cells grow to very low density

Product concentration low: Several mg to 100 g/L

Minimizing oxygen demand for aerobic cells & reducing Quorum sensing effects

Discontinuous processing

Contamination concerns

Developing continuous process

Sterilization costs high

High pressed steam

Contamination resisting strains grown in open systems

High energy demand for intensive aeration

Aerobic microorganisms need a lot of oxygen for growth

Developing anaerobic bioprocesses

Difficulty to control the bio-processes

Complicated cellular metabolisms

Artificial cells that contain only necessary metabolic pathways

One product by one microbial organism

Different organism has different strength.

Development of a platform organism for many products

Organisms consume food related products

Food for Fuels (Chemicals)

Kitchen wastes or activated sludge as substrates

Production facility costly

Costly materials and sensors

The use of carbon steel facilities et al.

Combination of bio- and chemical processes can offer a lot of advantages including bio-based (CO2 reduction) and fast reaction. Typical example includes the bio-production of lactic acid from anaerobic fermentation that is very effective and has only one single lactic acid product, and chemical polymerization of lactide to polylactide (PLA), a biodegradable green plastic[2, 13]. The PLA story is a successful combination of bio- and chemical advantages. Others like succinic acid and 1,4-butanol bio-production and their copolymerization are under intensive R&D[2, 13]. However, at the end, commercial successes have to be dependent on economy.



The author of this article is supported by grants from the State Basic Science Foundation 973 (Grant No. 2012CB725201) and State Industrialization Project (Grant No. 2012BAD32B02).

Authors’ Affiliations

MOE Key Lab of Bioinformatics and Systems Biology, Department of Biological Science and Biotechnology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China
Center for Nano and Micro Mechanics, Tsinghua University, Beijing, 100084, China


  1. Chen GQ, Kazlauskas R: Chemical biotechnology in progress. Curr Opin Biotechnol. 2011, 22: 1-2. 10.1016/j.copbio.2010.12.002View ArticleGoogle Scholar
  2. Chen GQ, Patel M: Plastics derived from biological sources: Present and future - A technical and an environmental review. Chemical Rev. 2012, 112: 2082-2099. 10.1021/cr200162d.View ArticleGoogle Scholar
  3. Chen GQ: A Polyhydroxyalkanoates Based Bio- and Materials Industry. Chem Soc Rev. 2009, 38: 2434-2446. 10.1039/b812677cView ArticleGoogle Scholar
  4. Gao X, Chen JC, Wu Q, Chen GQ: Polyhydroxyalkanoates as a source of chemicals, polymers and biofuels. Curr Opin Biotechnol. 2011, 22: 1-7. 10.1016/j.copbio.2010.12.002View ArticleGoogle Scholar
  5. Hemple F, Bozarth AS, Lindenkamp N, Klingl A, Zauner S, Linne U, Steinbuchel A, Maier UG: Microalgae as bioreactor for bioplastic production. Microb Cell Fact. 2011. 10. 81.View ArticleGoogle Scholar
  6. Tripathi L, Wu LP, Chen GQ: Microbial synthesis of diblock copolymer poly-3-hydroxybutyrate-block-poly-3-Hydroxyhexanoate [P(3HB)-b-P(3HHx)] by a genome reduced Pseudomonas putida KT2442. Microb Cell Fact. 2012, 11: 44- 10.1186/1475-2859-11-44View ArticleGoogle Scholar
  7. Zhou XY, Yuan XX, Shi ZY, Meng DC, Jiang WJ, Wu LP, Wu Q, Chen JC, Chen GQ: Hyperproduction of poly(4-hydroxybutyrate) from glucose by recombinant E. coli. Microb Cell Fact. 2012, 11: 54- 10.1186/1475-2859-11-54View ArticleGoogle Scholar
  8. Zhang S, Wang ZH, Chen GQ: Microbial polyhydroxyalkanote synthesis repression protein PhaR as an affinity tag for recombinant protein purification. Microb Cell Fact. 2010, 9: 28- 10.1186/1475-2859-9-28View ArticleGoogle Scholar
  9. Wang ZH, Ma P, Chen J, Zhang J, Yao YC, Zhang HF, Chen GQ: A heterogeneous two-hybrid system in Escherichia coli based on polyhydroxyalkanoates synthesis regulatory proteins PhaR. Microb Cell Fact. 2011. 10. 21.View ArticleGoogle Scholar
  10. Zhang XJ, Luo RC, Wang Z, Deng Y, Chen GQ: Applications of (R)-3-hydroxyalkanoate Methyl Esters Derived from Microbial Polyhydroxyalkanoates as Novel Biofuel. Biomacromolecules. 2009. 10. 707-711.View ArticleGoogle Scholar
  11. Tan D, Xue YS, Gulsimay , Chen GQ: Unsterile and Continuous Production of Polyhydroxybutyrate by Halomonas TD01. Bioresource Technol. 2011. 10.: 8130-8136.View ArticleGoogle Scholar
  12. Johnson K, Jiang Y, Kleerebezem R, Muyzer G, van Loosdrecht MCM: Enrichment of a Mixed Bacterial Culture with a High Polyhydroxyalkanoate Storage Capacity. Biomacromolecules. 2009. 10. 670-676.View ArticleGoogle Scholar
  13. Lee JW, Kim HU, Choi S, Yi J, Lee SY: Microbial production of building block chemicals and polymers. Curr Opin Biotechnol. 2011, 22: 758-767. 10.1016/j.copbio.2011.02.011View ArticleGoogle Scholar


© Chen; licensee BioMed Central Ltd. 2012

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