New challenges and opportunities for industrial biotechnology

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.

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. 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. The exhaustion of petroleum seems to be a remote reality 3. Agriculture raw materials for bioprocessing are becoming increasingly costly 4. Low cost raw material cellulose can not be easily used for microbial processes at least for the next 5-10 years 5. Bioprocessing is still not as effective as chemical processing, resulting in high cost of bio-products (Table 1) 6. Bioprocessing that requires large amount of fresh water has had increasing concerns in many water shortage areas 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 petrochemicals 8. The rapid development of C1 chemical engineering products 9. Large amount of funding is not more directed to industrial biotechnology.
Taking the example of polyhydroxyalkanoates (PHA), a biopolyester family that has been exploited to become an industrial value chain [2][3][4], 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 CO 2 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 ( Table 1).
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 ( Table 2). 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 [10][11][12]. 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 ( Table 2).
Combination of bio-and chemical processes can offer a lot of advantages including bio-based (CO 2 reduction) and fast reaction. Typical example includes the bioproduction 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.