Jw. Frost et Km. Draths, BIOCATALYTIC SYNTHESES OF AROMATICS FROM D-GLUCOSE - RENEWABLE MICROBIAL SOURCES OF AROMATIC-COMPOUNDS, Annual review of microbiology, 49, 1995, pp. 557-579
Chemistry is moving into a new era in which renewable resources and st
arting materials such as D-glucose will likely be prominent features o
f industrial chemical manufacture. The keys to this progress are the d
esign, development, and use of microbial biocatalysts. Aromatic biosyn
thesis serves as a paradigm for how biocatalysts can be manipulated to
achieve the yield, rate, and purity criteria central to chemical manu
facture. A disproportionate amount of the metabolic carbon flow of the
biocatalyst must first be directed into the common pathway of aromati
c amino acid biosynthesis. This review describes ways of achieving thi
s goal through the traditional strategy of manipulating the catalytic
activity of the first enzyme in the common pathway, as well as the ame
lioration of limitations in the in vivo availability of common-pathway
enzyme substrates. The inability of individual enzymes to convert the
ir substrate to product fast enough to avoid substrate accumulation fu
rther impedes carbon flow through the common pathway. This review also
discusses identification and removal of these rate-limiting enzymes.
Finally, we examine the creation of heterologous biocatalysts and how
biocatalysis could be integrated with traditional chemical transformat
ions to expand the number of organic chemicals that can be synthesized
from glucose.