ABSTRACT

There is a growing need for more sustainable approaches to the

manufacture of fine chemicals for pharmaceutical and agrochemical

agents.1 Of particular note is the challenge associated with the

manufacture of chiral chemicals in an environmentally sound

way. Traditional approaches to the asymmetric synthesis of chiral

compounds often involve the use of resolving agents, stochiometric

chiral reagents (e.g., chiral hydrides), auxiliaries, or catalysts

dependent upon chiral ligands and heavy metals such as rhodium

and ruthenium. The use of such reagents to induce asymmetry in

a molecule is not truly sustainable, and such processes often suffer

from less-than-perfect enantioselectivities, giving products that

require yield-eroding upgrading via recrystallization, or demand

reaction conditions that require specialized plant equipment for

operation, for example, high pressures and/or temperatures. In

contrast, biocatalysts offer an attractive combination of exquisite

selectivity and true sustainability, being biodegradable proteins pro-

duced from renewable resources. Directed evolution technologies

developed in the early 1990s enabled the optimization of enzymes to

function optimally in the desired process and provided a boost to the

field.2 This chapter aims to first introduce biocatalysis and directed

evolution technologies and then give specific case studies on the

development of efficient, sustainable, green-by-design biocatalytic

processes.