Green manufacturing from the deep blue sea
pharmafile | August 12, 2009 | News story | Manufacturing and Production |Â Â IngenzaÂ
UK researchers have embarked on a project to analyse marine microorganisms for enzymes that could be used to manufacture chiral pharmaceuticals and other fine chemicals in a more environmentally-friendly way.
The project is being carried out by UK company Ingenza Ltd along with scientists from Heriot-Watt University in Scotland and the Plymouth Marine Laboratory, and could in time help find more efficient and greener ways to manufacture new drugs for conditions such as epilepsy, diabetes, flu and other viruses.
The pharmaceutical sector is recognised as one which has a long way to go to improve its green credentials, according to the E-factor, a measure developed 17 years ago by Roger Sheldon of Delft University in the Netherlands.
The E-factor rates a chemical manufacturing route according to the ratio of waste to end-product. Bulk chemicals tend to have an E-factor below five; for fine chemicals the typical range is 5 to 50, and for some pharmaceuticals it ranges from 25 to 100 or more.
One reason for those high values is that pharmaceutical syntheses tend to be inefficient, and using new and improved catalysts to drive chemical reactions is one way to address that inefficiency. Catalysts which operate at lower temperatures and pressures and do not produce the same levels of waste by-products can also have a dramatic impact on production costs.
Dr Robert Speight of Ingenza says that the new project will look for improved catalysts by "taking advantage of the natural diversity of marine organisms that has arisen through evolution in different environments and coupling that with high-tech screening systems".
The scientists are looking for microbes that already have a built-in capacity to do the chemical reactions important to the industry, and in particular to create pure chiral molecules. From them they hope to isolate enzymes which can convert compounds that would have previously been waste products in the manufacturing process, into the desired product.
Organic compounds tend to exist in two mirror image forms or optical enantiomers. Whether a compound is optically left or right 'handed' has a major impact on its pharmacological activity. Since almost 50% of all new drugs contain at least one chiral centre, the new technology has potential to deliver major savings to the pharmaceutical industry.
A number of companies are trying to discover and develop new catalysts using approaches such as database mining and sequence alignments, but these do not guarantee that the enzymes found will have the desired activity. With their screening-based approach, the Ingenza and academic researchers start identify enzymes with the requisite activity first, which can then be modified to be suitable for industrial-scale use.
Ingenza's core expertise lies in separating and purifying chiral molecules via a process known as deracemisation, in which the unwanted enantiomer is converted to the desired form. The first target of the project is to discover novel amine oxidases, which are widely used in deracemisation reactions.
"The outcomes of this project will offer us is the chance to have a significant impact on the sustainability of pharmaceutical and biochemicals production as we move from oil-based to photosynthesis-derived chemistry," said Professor Doug Kell, chief executive of the Biotechnology and Biosciences Research Council.
Meanwhile, Ingenza is also working with Scottish drug discovery company Aquapharm to screen its collection of over 4,000 marine microorganisms for potential biocatalysts.
