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Metabolic Engineering 403

xylose, which is present in plant material as part of the By transforming a strain of P. chrysogenum with genes
heterogeneous polymer hemicellulose. Hemicellulose is encoding an expandase from Streptomyces clavuligerus,
one of the main constituents of lignocellulose, which due it has been possible to produce adipoyl-7-ADCA directly
to its abundance and low cost is an attractive raw material by fermentation with transformed strains of P. chryso-
for low value added products, e.g., fuel ethanol. genum (see Fig. 11). Similarly, it is possible to produce
adipoyl-7-ACA directly be fermentation with a recombi-
nant strain of P. chrysogenum harbouring genes encoding
C. Pathways Leading to New Products
the expandase/hydroxylase and the acyltransferase from
Metabolic engineering offers immense possibilities for Acremonium chrysogenum (see Fig. 11). From adipoyl-
constructingpathwaysleadingtonovelproducts,andthere 7-ADCA and adipoyl-7-ACA the compounds 7-ADCA
are many beautiful examples in the literature. There may and 7-ACA can easily be synthesised by enzymatic
be three different objectives for extending pathways to removal of the adipoyl side chain. This process of direct
produce new products in a certain organism: production of 7-ADCA and 7-ACA by fermentation
clearly demonstrates the potential of metabolic engineer-
Production of completely new compounds: This is of ing in the design of new processes, which is economically

particular importance in the field of pharmaceuticals, more efficient and more environmentally friendly than
where artificial pathways may produce new antibiotics the chemical synthesis route.
and anticancer drugs. However, also in the field of
materials it may be possible to tailor-make plastics
with specific properties. D. Pathways for Degradation of Xenobiotics
Through introduction of new pathways in a given

Bioremediation in the field of environmental cleanup has
microorganism, it may become possible to develop
attained much attention since the late 1980s. Bioremedia-
biotech-based process that can replace classical
tion refers to the use of natural microorganisms for reme-
chemical processes. This is primarily of interest since
diation of polluted air, water, soil, or sediment. Many field
biotech processes are more environmentally friendly,
tests and laboratory experiments have identified microor-
but also the selectivity of biochemical reactions may
ganisms that can degrade harmful organic compounds—
offer the possibility to produce optically pure
often referred to as xenobiotics—like aromatics (e.g.,
compounds more efficiently. Since biotech processes
benzene, toluene, xylene), halogenated aromatics (e.g.,
use sustainable raw materials and generally are more
polychlorinated biphenyls), halogenated aliphatics, and
environmentally friendly than chemical synthesis,
pesticides. However, there are two major problems in con-
these are often referred to as green chemistry.
nection with wide range application of these microorgan-
Exploitation of a common host for production of many

isms for biodegradation of xenobiotics:
different products: Thus it is possible to capitalize
investments in optimizing the fermentation process
with the general host. This is especially exploited in The rate of degradation is slow. This is mainly due to
the field of enzyme production, where a few host the fact that contaminants are often distributed over a
systems are applied to produce a wide range of wide range, and are present in too low concentrations
enzymes. Also, in the field of amino acid production to induce the degradation pathways.
there is focus on applying a few production systems, Degradation of mixtures of xenobiotics requires
i.e., E. coli and C. glutamicum. several different microbial species.
One area that illustrates the power of metabolic engi-
Metabolic engineering may be used to solve these prob-
neeringisthedevelopmentofalternativeroutesforthepro-
lems, and it furthermore offers the possibility to construct
duction of 7-amino cephalosporanic acid (7-ACA) and 7-
completelynovelxenobioticsdegradingpathwaysthrough
amino deacetoxycephalosporanic acid (7-ADCA), which
recruitment of enzymes from different organisms.
serves as precursors for the production of semisynthetic
cephalosporins. Until recently the sole route for 7-ADCA E. Engineering of Cellular Physiology
was by chemical ring expansion of 6-amino penicillanic for Process Improvement
acid (6-APA), which can be derived from penicillins.
Thus, many semisynthetic cephalosporins were tradition- In the industrial exploitation of living cells, their proper-
ally derived from penicillin produced by fermentation. ties may be undesirable, and it is therefore of interest to
With the high potential of β-lactam production by P. obtain cells with improved properties through metabolic
chrysogenum, it is of interest to engineer this organism engineering of the overall physiology of the cell. Some
to produce the cephalosporins directly by fermentation. typical problems encountered are as follows: