NEWS OF THE WEEK
MAMMALIAN PROTEIN: Secretion gained in filamentous fungi Researchers at Genencor Inc. have developed a secretion system for the products of mammalian genes in filamentous fungi. According to Genencor, one protein that has been produced using the new technology is the enzyme rennin, used in the production of cheese. The company believes that the system will be applicable to other industrial enzymes. Commercial production of rennin using recombinant DNA techniques has been a target of a number of biotechnology firms, says Genencor vice president of research Herbert L. Heyneker. Rennin is the enzyme used in cheese production that causes coagulation of milk solids into curds. Currently, rennin is obtained from calves' stomachs. South San Francisco-based Genencor has produced recombinantDNA rennin in Escherichia coli. Other biotechnology companies have produced it in E. coli, yeast, and other expression systems. The problem with such systems, Heyneker says, is that rennin is expressed in active form only in low yields. Inactive rennin can be produced in large quantities, but it must be treated by a costly renaturation process to obtain enzymic activity. Such rennin cannot compete economically with calf rennin. The problem is one that is common to a number of complex proteins whose conformation is determined in part by formation of one or more disulfide bonds. Such proteins are secreted by the mammalian cells that produce them naturally and the disulfide bonds form either during the secretion process or in the extracellular medium. When these proteins are produced in a microorganism and not secreted, the proper disulfide bonds often do not form, and the protein 4
September 9, 1985 C&EN
assumes an inactive conformation. Active protein can be obtained by renaturing the inactive protein. For some proteins, that process works quite well, Heyneker says. For rennin and a number of other mammalian proteins, however, it is inefficient and costly. One way around the problem is to produce the protein in an organism that subsequently secretes it. That has been done in mammalian cell culture but, as Heyneker points out, use of such cultures is a technological challenge in itself. Genencor turned to filamentous fungi because these organisms are known to secrete a large number of proteins naturally. The company already produces commercial foodgrade enzymes by large-scale fermentation of a number of species of filamentous fungi. Expression of the rennin gene and secretion of active rennin were achieved in an Aspergillus species
U.K. company bids $893 million for SCM In a sharp increase of its unsolicited takeover bid, Hanson Trust, a British conglomerate, offered $893 million last week to buy SCM Corp. The $72-per-share offer came a few days after a group of SCM executives and a unit of Merrill Lynch, Pierce, Fenner & Smith announced a leveraged buyout offer at $70 per share. Hanson Trust's latest offer puts pressure on Merrill Lynch Capital Markets either to top the British firm's figure or to drop out of the bidding. And since SCM's top management already had endorsed the adequacy of the $70-per-share offer through its involvement in the
of filamentous fungi, representing the first time a mammalian gene has been expressed in such an organism, Heyneker says. Genencor has filed for a patent on the technology. Another advantage of filamentous fungi is that many have a long history of use in the production of food-grade proteins. That should make obtaining regulatory approval for the use of recombinant proteins produced in filamentous fungi relatively straightforward. According to Genencor spokesman Jonathan MacQuitty, the firm believes the technology can be applied to a number of other recombinant proteins. One of the reasons why the industrial application of biotechnology has lagged behind, for example, pharmaceutical applications has been the absence of low-cost production systems, he says. Genencor believes that filamentous fungi might provide such a system. D
SCM at a glance Sales: $2.18 billion (fiscal 1985, ended June 30) Net income: $56 million Profit margin: 2.6% Saies by business segment: Chemicals $539 million (25%), coatings and resins $687 million (32%), paper products $362 million (16%), foods $422 million (19%), typewriters $176 million (8%) Operating profit by business segment: Chemicals $74 million, coatings and resins $50 million, paper products $23 million, foods $23 million, typewriters $47 million loss, including charge of about $35 million
