Jaume Mir

Mir, Jaume

Hemeroteca Cientifica Catalana

EDITORIALIndustrial microbiology. A new challengeTogether with metallurgical processes, microbiology is thetechnological and scientific field that has been used fromancient times both to improve living conditions and to in-crease survival opportunities by transforming risks into chal-lenges. After humans became sedentary, and agriculture be-gan to transform food availability, acquiring new materialsthat either never existed before (metallurgy) or existed atvery low levels (microbiology) became the impetus for a newhuman activity: industry. Industry has been usually definedas the art and ability to transform raw materials into new anduseful products. Food was most likely one of the first prod-ucts that humans tried to ensure. While agriculture gavehumans the possibility of having enough food, weather andclimatic conditions limited its year-round availability. Thus,the challenge was being able to maintain sufficient foodstocks in good condition throughout the year, until the nextharvest. Microbiology was involved in this process bychance and, as a result (probably after hundreds of failedattempts), bread, cheese, wine and beer have been consumedfor thousands of years. In fact, yeast was used to producebeer in Sumeria before 7000 BC, and Assyrians already pro-duced wine in 3500 BC. These beverages are obtained throughthe action of microorganisms, and the final products can bestored for longer periods than the original raw materials. Twomain characteristics defined early industrial processes: (i)They appeared after a coincidental observation (i.e. the fer-mentation of sugar present in fruits or grains to yield alco-hol), which human societies then gradually learnt to controland to make more profitable. (ii) Although processes derivedfrom these observations were optimized and became increas-ingly profitable, knowledge of them was a result of experi-ence, and the reasons why, e.g., fruit must turned into wine ormilk turned into cheese, were not known.Such was the state-of-the-art until the second half of thenineteenth century, when two events marked the beginning ofindustrial microbiology: (i) The scientific phenomena res-ponsible for early industrial processes started to be under-stood and well known. Around 1860, Pasteur discovered themajor role of yeast in the food and beverage industries. As aresult, he has been considered the father of modern microbi-ology. The idea that microorganisms were living material thatcould be used as elementary chemical reactors became wide-ly accepted. Thus, industrial microbiologists could addressthe same concepts as engineering chemists (especially ener-gy and mass balances). (ii) The capability to control andmake these processes much more profitable (including theuse of more efficient microbial species or strains) increased.This capability derived from the recognition that the condi-tions at which microbial “machines” give an optimal yield arecontrolled, external ones (pH, temperature, pressure, feedflow) that do not affect the machine itself: the microorgan-isms used grow also naturally in the environment. Further-more, all the processes focus on maintaining the status quo,trying to avoid variations that might affect the yield. Eventoday, some of the regulations for whisky and wine produc-tion are related to the need to use endogamic yeast. There-fore, mutation, degradation or contamination of the workingmicrobial species are risks to be avoided.That had been the situation until a few decades ago, andis the core of classic industrial microbiology [3]. Microbialprocesses are involved in food, pharmaceutical, fine-chemi-cal, cosmetic, energy and new-material industries. It has beenestimated that these processes move currently more than US$70 billion worldwide [1]. The replacement of petroleum-basedfuels by yeast fermentation-obtained ethanol (bioethanol)will mean a new revolution in the energy market and it willfulfill environmental requirements. For several reasons,microbiological processes with industrial applications areusually much more advantageous than any other industrialprocesses, accounting for the strong continued interest in thisfield. First, the specific ability of a given microorganism toproduce a particular molecule can be exploited. This mole-cule can be a secondary metabolite or, more directly, a by-product of microbial metabolism. While chemical industrialprocesses may yield the same product, the process is oftenmore complex, involving more pathway steps, and/or mixedwith some undesirable byproducts. Second, the moleculesobtained from microorganisms are synthesized under mildJaume MirAbengoa Bioenergy, Bioetanol Galicia,Teixeiro, SpainINTERNATIONAL MICROBIOLOGY (2004) 7:81–82 www.im.microbios.orgE-mail: jaume.mir@bioetanolgalicia.abengoa.com82 INT. MICROBIOL. Vol. 7, 2004conditions, resulting in less energy and equipment costs com-pared with chemical synthetic processes. Nevertheless,industrial microbiology still has some limitations, due to theneed of having the working microorganism fully operativeand protected against mutation, other microbial contami-nants, competitors, and environmental changes.During the last few decades, molecular biology and sub-sequently genetic engineering have contributed to a betterunderstanding of both the ultimate mechanisms involved inindustrial microbial processes and the main conditions influ-encing them. For the first time, it has been possible to modi-fy selectively and efficiently these microbiological machines;their natural abilities have been improved or new onesderived from other organisms (either microbes or evenplants) have been added to them. As a consequence, these liv-ing machines have turned out to be more productive andmore resistant against changes, and can thus be used for othernew biochemical reactions.Over the last 20 years, new or more efficient industrialprocesses involving microorganisms have been launched,yielding purer, less expensive products or substances notavailable using classical chemical methods. In general, it isnow possible to: (i) convert secondary reactions into mainmetabolic pathways; (ii) optimize productions and yields;(iii) change the original metabolic pathways to allow the useof less expensive raw materials, or to obtain previouslyunknown molecules; and (iv) use the enantiomeric propertiesof enzymes to obtain new chiral molecules. The long list ofproducts obtained by these methods increases every year, andmany industrial areas are involved. The products most com-monly obtained in industrial microbiology include:• Pharmaceutical proteins (human interferon, epidermalgrowth factor and hemoglobin, antigens for hepatitis-Bvirus, stabilizers for erythropoietin and human chorionicgonadotropin) obtained from microorganisms such asSaccharomyces cerevisiae, Pichia pastoris, Hansenulapolymorpha or Agrobacterium tumefaciens.• Recombinant enzymes for industrial processes obtainedfrom microorganisms. The industrial enzyme market fornon-therapeutic uses, such as food, detergents, textiles,leather, pulp and paper industry reached US $2 billion in2000 [2]. Microbial lipases are of special interest becauseof their stability in organic solvents and their lack of arequirement for cofactors, their broad substrate specifici-ty and their high enantioselectivity. Lipolase™ fromNovozyme, launched in 1994, is the first recombinantlipase; it was obtained by cloning the Thermomyceslanuginosus (formerly Humicula lanuginosa) lipase geneinto the Aspergillus orzyae genome [4].• Antibiotics, including biosynthetic penicillin V and natu-ral penicillin G. Of the 12,000 antibiotics known in 1995,more than 20% can be produced by filamentous fungi.Biosynthetic and semisynthetic penicillins and cefalospo-rins have a market reaching US $15,4 billion. • Inmunosuppresive agents, including cyclosporin A, ob-tained from Tolypocladium nivenum, or mycophenolatemofetil, from several Penicillium species.• Hypocholesterolemic agents including lovastatin, obtainedfrom Aspergillus terreus, and pravastatin, from Penicilliumcitrium, which have a market of US $15 billion.• Antitumoral agents such as taxol, first discovered inplants but later transferred to and produced by Taxomycesandreanae; in 2000 it comprised 10% of total sales forBristol Myers-Squibb, reaching US $1 billion [5].• Mycotoxins including adrenalin inhibitors, estrogens andanabolic agents for cattle and sheep, or gibberellins usedin brewing and malting industries.• Pigments, including the carotenoid astaxanthin fromPhaffia rhodozyma, and β-carotenoid from Blakesleatrispora, used in food and textile industries.• Polyunsaturated fatty acids, including γ-linoleic acidfrom Mucor circinelloides, and arachidonic acid fromMortierella isabellina. This voyage is only at its beginnings, and many challengesstill face us. For example, the technology suitable to synthe-size all these molecules in a less expensive, more efficientway, using carbon dioxide as the carbon source, water as theelectron acceptor, and sunlight as the driving energy, is need-ed. Many scientists have tried to solve this equation for years,unaware that such a process namely, photosynthesis, alreadyexists and has been used by photosynthetic organisms (manymicroorganisms and all plants) for millions of years. As afinal example, the previously mentioned switch from petrole-um-based fuels to bioethanol will mean a new revolution inthe energy market, and will change significantly internation-al commercial relationships. Nevertheless, this is only thefirst step towards the final goal: the hydrogen-based battery.Microbiology will no doubt take part in this task as well.References1. Adrio JL, Demain AL (2003) Fungal biotechnology. Int Microbiol6:191–1992. Carlsen S (1990) Molecular biology in research and production ofindustrial enzymes. In: Wolnak B, Scher M (eds) Industrial use ofenzymes; technical and economic barriers. Brenard Wolnak, Chicago,pp 52–693. Demain AL (1996) Fungal secondary metabolism: regulation and func-tions. In: Sutton B (ed) A century of mycology. Cambridge Univ. Press,Cambridge, MA, pp 233–2544. Strohl WR (1997) Industrial antibiotics: today and the future. In: StrohlWR (ed) Biotechnology of antibiotics, 2nd ed. Marcel Dekker, NewYork, pp 1–47MIR

Industrial microbiology. A new challenge

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