Fundamental Biochemical and Biotechnological Principles of Biomass Growth and Use 23

1.3.9.4 Pharmaceuticals

The pioneering role of the antibiotic penicillin has already been acknowledged earlier

in this chapter. Drugs are still one of the most relevant and profitable applications of

fermentative microbial transformation. The regular carbon source is sugar, which is

easily taken up and metabolized by the transforming organism. Today 20% of commer-

cial drugs and 50% of drugs under development (Bonnacorso, 2014) are estimated to

be produced by biotechnology.

Still relevant are antibiotics of theβ-lactam type produced by the fungiPenicillium

(penicillin) andCephalosporium (cephalosporins). The appearance of resistances

initiated the development of derivatives of the natural molecules by adding chemically

a wide variety of side chains to the microbial nucleic molecule. The estimated world

market is some 10,000 tons (Table 1.24).

A modern group of biopharmaceuticals are monoclonal antibodies (mAbs). The

production method of these highly functional proteins is based on the scientific work

of the German biologist Georges J.F. Köhler (1946–1995) and the Argentinian chemist

César Milstein (1927–2002) at Cambridge University (Great Britain) who both received

the Nobel Prize in 1984. They fused antibody-producing B-cells with myeloma cells

to the so-called hybridoma cells. By this method, clones of cells producing identical

mAbs are propagated. The mAbs are highly active drugs that are used at a daily dose

in microgram range. Though produced rather in kilogram than in ton range, the global

sales volume is about $40 billion with an annual growth rate of 9% (Table 1.25).

Obviously, there are much more pharmaceuticals, but as drugs are not the main topic

of this chapter the examples of antibiotics and mAbs should be sufficient to demonstrate

(i) the high value and (ii) the low volume (and feedstock demand) of pharmaceuticals.

Table 1.24Some semisynthetic antibiotics and their global annual production volume (Franssen,

Kircher, and Wohlgemuth, 2010).

Antibiotic Nucleus Side chain ton year−^1

Ampillicin 6-Aminopenicillanic acid d-Phenylglycine 5000

Cephalexin 7-Aminodeacetoxycephalosporanic acid d-Phenylglycine 4000

Amoxicillin 6-Aminopenicillanic acid d-Hydroxyphenylglycine 16,000

Cefadroxil 7-Aminodeacetoxycephalosporanic acid d-Hydroxyphenylglycine 1000

Table 1.25Indications to be treated by monoclonal antibodies and sales volume (Pohl-Appel, 2011).

Monoclonal antibody Indication Company Sales (billion US$)

Rituximab MabThera®/Rituxan® Rheumatoid arthritis Hoffmann-La Roche 4.1 (1998)

Trastuzumab Herceptin

®

Cancer Hoffmann-La Roche 3.6 (2000)

Adalimumab Humira® Rheumatoid arthritis Abbott Laboratories 4.5 (2003)

Cetuximab Erbitux

®

Cancer Merck Serono 0.9 (2004)

Bevacizumab Avastin® Cancer Hoffmann-La Roche 4.2 (2005)