Biotechnology can do it
A breakthrough at Wacker – using fermentation to make cysteine

Hair, feathers and pig bristles: until recently, the amino acid cysteine was extracted from human and animal sources. The latest advances in biotechnology now give the pharmaceutical industry a completely new source of this indispensable raw material. Wacker uses a fermentation process to produce super-pure cysteine from bacteria.

Winter is the high season for colds. You hear people coughing and clearing their throats all around you in an attempt to remove mucous from their respiratory passages. A lot of people buy medication from their local pharmacy to loosen the mucous and make it easier to cough up. Acetylcysteine is a well-known active ingredient, but few patients with respiratory congestion are aware of the fact that they are swallowing a substance which is extracted from a material that they are very familiar with and which is used in many other items including breakfast rolls, pizza and products used by hairdressers or as artificial meat flavoring in vegetarian food. Acetylcysteine is based on the amino acid cysteine, one of 20 building blocks which make up the protein alphabet (please refer to the information in the box). However, there is one serious impediment to the widespread use of this sulfurous amino acid. Until recently, it was one of the few amino acids which had to be extracted from human or animal “raw materials” such as hair, feathers, pig bristles or hooves. Extraction has become a fully-fledged industry in Asia. Every year, tens of thousands of tons of hair are collected at Chinese hairdressers and delivered to cysteine producers, who extract the sought-after amino acid using activated charcoal and concentrated hydrochloric acid. It takes one ton of hair to produce 100 kilograms of cysteine.

“When you consider that annual demand for cysteine in the pharmaceutical, cosmetics and food industries can be as high as 4,000 tons, you can imagine how much raw material is needed,” explained Christoph Winterhalter who is the Cysteine Project Manager at Wacker Specialities. Yet the need for greater efficiency and reduction in the environmental impact were not even the most important reasons for developing an alternative production method. The quality of the product was an even more compelling reason in many applications. Winterhalter continued: “Pharmaceutical companies absolutely must eliminate any possibility of dangerous contamination, for example from BSE, SARS or avian influenza pathogens, and our process does just that. We are the only company worldwide which is able to produce super-pure cysteine using a fermentation process.” The company uses “laboratory animals” (escherichia coli cultures), which are commonly found at biotech companies, to provide the basic raw material. Even in nature, these bacteria make cysteine from sugar, salts and trace elements, but they only produce the amounts that they need for their own metabolism.
Targeted mutation and selection
Using targeted mutation and selection, researchers at Wacker were able to shut off so-called regulator proteins which normally limit production of cysteine in the bacteria. As a result, the bacteria now “mass produce” cysteine. The excess amino acid passes through the cell membrane into the nutrient solution in the fermentation tanks. A filtration process and small amounts of acid and alkali are used to extract the amino acids as well as target derivatives. This method has a number of advantages:
-It is highly efficient. Ninety percent of the bacterial cysteine flows into the end product compared with only 60 percent with conventional extraction from hair. There is also a dramatic reduction in the amount of hydrochloric acid used during production. It only takes one kilogram of hydrochloric acid to produce one kilogram of cysteine compared to 27 kilograms of hydrochloric acid for one kilogram of cysteine when hair is used as the raw material.
-There is no unwanted contamination. No pathogens can get into the end product, because only sugar, salts and trace elements are used as raw materials. “Our product is at least 98.5% pure cysteine and meets the requirements of the food and pharmaceutical industries,” declared Winterhalter.
-The process does not use any foreign genetic material. The Central Commission for Biological Safety at the Robert Koch Institute in Berlin has confirmed that the E.coli culture has not been genetically modified. “The bacteria which we use belong to the most harmless class of organisms, similar to lactic acid bacteria,” explained Christoph Winterhalter. Five hundred tons of cysteine were produced in 2004 using the patented Wacker process and delivered to customers worldwide from the Burghausen plant. The customers are primarily in the pharmaceutical, food and cosmetic industries, and premium quality is very important to them. Winterhalter emphasized that “we are seeing an enormous increase in demand for our cysteine, and we will certainly expand the business in the future”.
This does not mean, however, that hair collection in Asia will cease immediately. Three thousand tons of cysteine are still extracted annually using the conventional method, but market share will change. The old production method will survive the longest where the lowest price rather than production origin is the most important factor in the customer’s purchase decision