Articulo microorganismos

Biotechnology Advances 18 (2000) 499–514

Research review paper

Small bugs, big business: The economic power of the microbe
Arnold L. Demain*
Fermentation Microbiology Laboratory, Department of Biology 68-223, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Abstract The versatility of microbial biosynthesis is enormous. The most industrially important primary metabolitesare the amino acids, nucleotides, vitamins, solvents, and organic acids. Millions of tons of amino acids are produced each year with a total multibillion dollar market. Many synthetic vitamin production processes are being replaced by microbial fermentations. In addition to the multiple reaction sequences of fermentations, microorganisms are extremely useful in carrying out biotransformationprocesses. These are becoming essential to the fine chemical industry in the production of singleisomer intermediates. Microbially produced secondary metabolites are extremely important to our health and nutrition. As a group, they have tremendous economic importance. The antibiotic market amounts to almost 30 billion dollars and includes about 160 antibiotics and derivatives such as the -lactampeptide antibiotics, the macrolide polyketide erythromycin, tetracyclines, aminoglycosides and others. Other important pharmaceutical products produced by microrganisms are hypocholesterolemic agents, enzyme inhibitors, immunosuppressants and antitumor compounds, some having markets of over 1 billion dollars per year. Agriculturally important secondary metabolites include coccidiostats, animal growthpromotants, antihelmintics and biopesticides. The modern biotechnology industry has made a major impact in the business world, biopharmaceuticals (recombinant protein drugs, vaccines and monoclonal antibodies) having a market of 15 billion dollars. Recombinant DNA technology has also produced a revolution in agriculture and has markedly increased markets for microbial enzymes. Molecularmanipulations have been added to mutational techniques as means of increasing titers and yields of microbial procresses and in discovery of new drugs. Today, microbiology is a major participant in global industry. The best is yet to come as microbes move into the environmental and energy sectors. © 2000 Elsevier Science Inc. All rights reserved.
Keywords: Biotechnology; Primary metabolites; Secondarymetabolites; Economics

* Corresponding author. Fax: 1-617-253-8699. E-mail address: demain@mit.edu (A.L. Demain). 0734-9750/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S 0 7 3 4 - 9 7 5 0 ( 0 0 ) 0 0 0 4 9 -5

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A.L. Demain / Biotechnology Advances 18 (2000) 499–514

1. Introduction For thousands of years, microorganisms have been used to supply us withproducts such as bread, beer, wine, distilled spirits, vinegar, cheese, pickles and other fermented materials. These processes were originally developed for the preservation of fruits, vegetables and milk, but developed into sophisticated products satisfying the palate and psyche of humans. A second phase of biotechnology began during World War I which resulted in a quantum jump in the economicimportance of microbes. In England, Chaim Weizmann developed the acetone-butanol fermentation and in Germany, the glycerol fermentation was formulated by Neuberg. Both acetone and glycerol were needed for manufacture of munitions to support the war efforts of the respective opposing nations. These events were followed after the war by development of fermentation, bioconversion, and enzymatic processesyielding many useful products with large annual markets. These include amino acids, nucleotides, vitamins, organic acids, solvents, vaccines and polysaccharides. A major segment of the second phase was represented by secondary metabolites such as antibiotics. Ever since the discovery of penicillin in 1929 and its commercial development starting at the beginning of World War II, antibiotic...