Small bugs, big business: the economic power of the microbe.

The versatility of microbial biosynthesis is enormous. The most industrially important primary metabolites are 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 biotransformation processes. These are becoming essential to the fine chemical industry in the production of single-isomer 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 beta-lactam peptide 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 growth promotants, 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. Molecular manipulations 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.

[1]  Michael Mccoy.  SETTING COURSE FOR PROSPERITY , 1999 .

[2]  A. Campbell,et al.  Genetic and biochemical characterization of the birA gene and its product: evidence for a direct role of biotin holoenzyme synthetase in repression of the biotin operon in Escherichia coli. , 1981, Journal of molecular biology.

[3]  A. Demain,et al.  Riboflavin oversynthesis. , 1972, Annual review of microbiology.

[4]  C. Gustafsson,et al.  Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Dudley H. Williams,et al.  The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria. , 1999, Angewandte Chemie.

[6]  A. Demain,et al.  Emerging Concepts of Secondary Metabolism in Actinomycetes , 1995 .

[7]  M. Ranke,et al.  5 Recombinant human growth hormone , 1986 .

[8]  M. Niwa,et al.  Cloning of genes coding for L-sorbose and L-sorbosone dehydrogenases from Gluconobacter oxydans and microbial production of 2-keto-L-gulonate, a precursor of L-ascorbic acid, in a recombinant G. oxydans strain , 1997, Applied and environmental microbiology.

[9]  W. H. Stroh.  INDUSTRIAL ENZYMES MARKET , 1998 .

[10]  D. Cowan.  Industrial enzyme technology , 1996 .

[11]  T. Beppu,et al.  Cloning of the Membrane-Bound Aldehyde Dehydrogenase Gene of Acetobacter polyoxogenes and Improvement of Acetic Acid Production by Use of the Cloned Gene , 1989, Applied and environmental microbiology.

[12]  L. Wackett.  Bacterial biocatalysis: Stealing a page from nature's book , 1997, Nature Biotechnology.

[13]  Y. Peleg,et al.  l-Malic acid formation by immobilized Saccharomyces cerevisiae amplified for fumarase , 1991 .

[14]  W. C. Wernau,et al.  A second branched-chain alpha-keto acid dehydrogenase gene cluster (bkdFGH) from Streptomyces avermitilis: its relationship to avermectin biosynthesis and the construction of a bkdF mutant suitable for the production of novel antiparasitic avermectins , 1995, Journal of bacteriology.

[15]  E. Vandamme,et al.  Production of vitamins, coenzymes and related biochemicals by biotechnological processes. , 2007, Journal of chemical technology and biotechnology.

[16]  L. Vining,et al.  Biosynthesis of gibberellins in Gibberella fujikuroi. Gibberellin A16. , 1973, Canadian journal of biochemistry.

[17]  Stephen Stinson,et al.  COUNTING ON CHIRAL DRUGS , 1998 .

[18]  J. Zeikus,et al.  Biotechnology of succinic acid production and markets for derived industrial products , 1999, Applied Microbiology and Biotechnology.

[19]  R. S. Rogers.  COMPANIES TURN TO BIOCATALYSIS , 1999 .

[20]  D. Wilke.  Chemicals from biotechnology: molecular plant genetics will challenge the chemical and the fermentation industry , 1999, Applied Microbiology and Biotechnology.

[21]  M. Doi,et al.  Effects of Homoserine Dehydrogenase Deficiency on Production of Cytidine by Mutants of Bacillus subtilis. , 1996, Bioscience, biotechnology, and biochemistry.

[22]  A. Kuninaka.  Nucleotides and Related Compounds , 2001 .

[23]  J. Handelsman,et al.  Zwittermicin A-producing strains of Bacillus cereus from diverse soils , 1994, Applied and environmental microbiology.

[24]  A. Demain,et al.  Betaine Stimulation of Vitamin B12 Biosynthesis in Pseudomonas denitrificans May Be Mediated by an Increase in Activity of δ-Aminolaevulinic Acid Synthase , 1984 .

[25]  M. Kikuchi,et al.  Cloning of the Bacillus Subtilis IMP Dehydrogenase Gene and its Application to Increased Production of Guanosine , 1986, Bio/Technology.

[26]  T. Tosa,et al.  Improvement of Nitrogen Supply for L-Threonine Production by a Recombinant Strain of Serratia marcescens , 1992, Applied biochemistry and biotechnology.

[27]  D. Hochstrasser,et al.  Biotin production under limiting growth conditions by Agrobacterium/Rhizobium HK4 transformed with a modified Escherichia coli bio operon , 1999, Journal of Industrial Microbiology and Biotechnology.

[28]  R Bentley,et al.  Secondary metabolite biosynthesis: the first century. , 1999, Critical reviews in biotechnology.

[29]  T. Goodson,et al.  Production of a hybrid macrolide antibiotic in Streptomyces ambofaciens and Streptomyces lividans by introduction of a cloned carbomycin biosynthetic gene from Streptomyces thermotolerans. , 1989, Gene.

[30]  P. Skatrud,et al.  Use of Recombinant DNA to Improve Production of Cephalosporin C By Cephalosporium acremonium , 1989, Bio/Technology.

[31]  K. Chater.  The Improving Prospects for Yield Increase by Genetic Engineering in Antibiotic-Producing Streptomycetes , 1990, Bio/Technology.

[32]  A. H. Rose.  Primary products of metabolism , 1978 .

[33]  W. Campbell,et al.  Ivermectin: a potent new antiparasitic agent. , 1983, Science.

[34]  H. Haag,et al.  Section Review; Anti-infectives: Review of actinomycetes compounds 1990 – 1995 , 1996 .

[35]  Michael C. Flickinger,et al.  Encyclopedia of bioprocess technology : fermentation, biocatalysis, and bioseparation , 1999 .

[36]  W. Strohl.  INDUSTRIAL ANTIBIOTICS : TODAY AND THE FUTURE , 1997 .

[37]  N. Sakurai,et al.  Further improvement of D-biotin production by a recombinant strain of Serratia marcescens , 1995 .

[38]  B. Tudzynski.  Biosynthesis of gibberellins in Gibberella fujikuroi: biomolecular aspects , 1999, Applied Microbiology and Biotechnology.

[39]  A. Endo,et al.  Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. , 1985, Journal of medicinal chemistry.

[40]  G. Hegeman,et al.  Genetics and Molecular Biology of Industrial Microorganisms , 1989 .

[41]  A. Demain.  5 – Production of Nucleotides by Micro-Organisms , 1978 .

[42]  H Umezawa,et al.  Low-molecular-weight enzyme inhibitors of microbial origin. , 1982, Annual review of microbiology.

[43]  C. Kao,et al.  Evolutionally guided enzyme design. , 1996, Biotechnology and bioengineering.

[44]  A. Neilson.  PAHs and Related Compounds , 1998 .

[45]  Helen A. Stafford,et al.  Secondary metabolites: Their function and evolution , 1993 .

[46]  G. Ferni,et al.  Microbial Production of Vitamin B12 , 1989 .

[47]  A. Demain.  New applications of microbial products. , 1983, Science.

[48]  I. Hillebrand,et al.  Microbial α-Glucosidase Inhibitors: Chemistry, Biochemistry, and Therapeutic Potential , 1988 .

[49]  Pascal Hols,et al.  Conversion of Lactococcus lactis from homolactic to homoalanine fermentation through metabolic engineering , 1999, Nature Biotechnology.

[50]  M. Payton,et al.  Conversion of Glucose to 2-Keto-l-Gulonate, an Intermediate in l-Ascorbate Synthesis, by a Recombinant Strain of Erwinia citreus , 1988, Applied and environmental microbiology.

[51]  J. Westley.  Polyether antibiotics: versatile carboxylic acid ionophores produced by Streptomyces. , 1977, Advances in applied microbiology.

[52]  Marc Reisch.  THE FIX IS IN: CARTELS BEWARE: U.S. regulators have targeted international price-fixing cartels, many selling chemical products , 2000 .

[53]  L. Ingram,et al.  Genetic engineering of ethanol production in Escherichia coli , 1987, Applied and environmental microbiology.

[54]  H. Sahm,et al.  l-Glutamate and l-lysine: traditional products with impetuous developments , 1999, Applied Microbiology and Biotechnology.