Is Thermo Fisher Scientific poised to become the savior of N-terminal sequencers?
On the heels of Applied Biosystems’ pullout from the Edman sequencing market, which left the United States without a player in the space, Thermo Fisher is at least exploring the possibility of entering the arena by developing its own Edman sequencer or an alternative technology, a company official told ProteoMonitor last week.
The process is still in its early days, and no decision has been reached yet on whether the company will definitively develop and manufacture such a technology, much less the iteration that a technology may take. But Andreas Huhmer, director marketing for proteomics for Thermo Fisher, said that although N-terminal sequencing is not a “rapidly growing market … it’s very clear to us at this point that the some of the needs in this market are not satisfied by current technologies.
“So we’re currently investigating whether we could serve those needs,” he said.
In late June, ABI joined the list of manufacturers that have pulled out of Edman sequencing when it stopped production of its Procise instrument, leaving the US market bereft of an Edman sequencing vendor. At the time, an official at ABI told ProteoMonitor that because of declining sales and the availability of other protein sequencing methods, it “no longer makes sense” to continue manufacturing the instrument, though the company would continue selling consumables for the Procise for an undisclosed period of time and had no plans to shutter that business [See PM 06/12/08].
The company, he added, would provide support to Procise users for “at least five years” after the shutdown. Nonetheless, ABI’s decision created a minor uproar with some researchers who faced a future without Edman sequencing.
Thermo Fisher first publicly indicated its interest in the space when a company official posted on the Association of Biomolecular Resource Facilities’ message board seeking feedback. The company, the post read, “is considering developing an alternative technology to the traditional protein sequencer/Edman sequencing. We are looking for individuals … [who] might be interested in talking to Thermo about this new technology.”
According to Huhmer, the company has received “enthusiastic response” to its inquiry.
“Most said, ‘Yeah, I’ve been doing sequencing for a long time. I think I feel pretty comfortable talking about [my] needs with you,’” he said, adding Thermo Fisher has begun has begun scheduling meetings with researchers.
In particular, he said, the company would like to work with members of ABRF’s Edman Sequencing Research Group to get their feedback.
“We will probably just mothball the sequencer if we cannot afford to get it repaired.”
The sentiments of that group regarding Thermo Fisher’s announcement is unclear. Six of the group’s seven members did not respond to requests for interviews. One member said he was aware of Thermo Fisher’s interest but did not know enough specifics to comment.
Indeed, Thermo Fisher’s level of commitment to enter the space is unclear, and Huhmer declined to say whether the company has made a final decision to move into protein sequencing or whether it is essentially on a reconnaissance mission at this point. He added that the company has set no deadline on any actions it may take.
He also said that it was premature to speculate about any technology that may be developed from a possible foray by Thermo Fisher into the space.
“At this point, where we’re gathering initial needs from the marketplace; it’s too early to specify any technology or any specific potential product,” he said.
If They Build it Will Anyone Buy it?
While Thermo Fisher’s mass specs have protein-sequencing capabilities, the company has never offered an Edman sequencer, and if it were to begin offering the technology now, it would be doing so at a time when demand for the instrument is waning.
Satya Yadav, director of the Molecular Biotechnology Core Laboratory at the Cleveland Clinic Lerner Research Institute, said that at his facility, demand for Edman sequencing has gone down “dramatically the last four years,” as mass specs have replaced them as the main instrument for protein sequencing.
Developed around 60 years ago, Edman sequencers were once the workhorse instrument of protein chemists, and at the height of its use several manufacturers such as Beckman Coulter, Agilent Technologies, and Hewlett Packard operated in the space.
But as newer protein-sequencing methods became popular, the technology gradually lost its cachet, and today it is viewed as something of a relic.
However, there remains a small but loyal community of protein researchers who say that the technology is unparalleled in its ability to provide unequivocal sequencing data, especially for N-terminal sequencing and de novo sequencing.
Other methods for protein sequencing include mass spec-based methods, but Edman sequencing loyalists say that mass spectrometry can generate data that is variable in quality and quantity and cannot distinguish between isobaric amino acids. MS/MS data, they add, typically do not contain structural information for the entire peptide.
Protein sequences can also be determined indirectly from the mRNA and DNA, but again, some guesswork is involved with such techniques, opening the door for human error.
One advantage of Edman sequencers is the “relative quantitative purity of protein” that it offers, said Ben Madden, staff scientist at the Mayo Proteomics Research Center at the Mayo Clinic.
“With mass spectrometry, it’s more difficult to quantitate the contaminants or to quantitate N-terminal heterogeneity [and] … you may or may not find the N-terminal peptide on a mass spectrometer,” he said.
His lab, which uses a Procise platform, runs about 30 to 40 samples each year, primarily for purity assessment, N-terminal processing of a particular protein, and antibody sequencing. While the demand for Edman sequencing is relatively low, Madden said that the machine still has its place in the protein research laboratory. But, he added that any technology that may be developed by Thermo Fisher would need to have other capabilities in order for it to be a justifiable purchase.
“If they’re going to make an instrument that does only protein sequencing, similar to Edman sequencing, then it can’t be a $200,000 instrument, because I don’t think people are going to see it as that important,” he said. “It would be nice if it could be … used for other things, but also did Edman sequencing, or something like Edman sequencing.”
Not everyone, however, believes that the technology serves much of a purpose any longer. The Cleveland Clinic’s Yadav has also owned a Procise platform for 10 years and said that if a time came when he would need to replace it with another Edman sequencer, he wouldn’t — particularly in times when budgets are tight.
He conceded that mass spectrometry is not suitable for N-terminal sequencing, but said that he would stop offering that service rather than invest in another Edman sequencer.
“We will probably just mothball the sequencer if we cannot afford to get it repaired,” he said.
Along with Thermo Fisher, another firm that may be looking to bring Edman sequencers to the US market is Shimadzu, which sells the PPSQ Series Protein Sequencer in Japan, but not in the US. In June, a company representative from US subsidiary told ProteoMonitor that it has been in discussions with its parent firm about bringing the machines across the Pacific, but no such decision had been made yet.
Company officials were not available for comment this week.