King Street Properties and Carlyle Group acquired 830 Winter St. in Waltham for $104.2 million, or $572 per foot, in a reflection of investor demand for biotech-leased office properties in core suburban markets.

Life science expansion is changing the DNA of Route 128 real estate as pharmaceutical giant Shire expands its Lexington campus and biotech startups circle office parks in Lexington and Waltham in search of lab space.

Shire is expected to fill a large office vacancy as it expands its Massachusetts workforce by 500 employees by the end of March. It has agreed to acquire the former Cubist Pharmaceuticals buildings at 45-55 Hayden Ave. in Lexington, which contain 190,000 square feet of office space on a 26-acre site, according to real estate sources.

That would enlarge what is already the suburbs’ largest biotech campus, with Shire already owning or leasing 900,000 square feet in eight buildings. The maker of ADHD drug Adderall is consolidating its Chesterbrook, Pennsylvania operations at a new U.S. headquarters in Lexington.

Since establishing its Lexington campus in 2008, Shire has solidified its commitment to the Greater Boston life science cluster. As of Dec. 31, it had 2,370 employees at facilities in Belmont, Cambridge, Lexington, North Reading and Waltham, an increase of nearly 1,000 in the past two years. It currently has 418 active job listings in Massachusetts, spokeswoman Katie Joyce said.

“We are reviewing our corporate, R&D and manufacturing space needs and anticipate that we will continue to grow in Massachusetts,” Joyce said.

Hartwell Avenue Attracting ‘Serious Interest’

Lexington officials are marketing the Hartwell Avenue corridor that runs parallel to Route 128 as another option for companies unable to find or afford space in Cambridge.

Approximately 150,000 square feet of lab space will be available this year at properties along Hartwell Avenue, said Melissa Tintocalis, Lexington’s economic development director. The town will consider offering tax increment financing agreements to developers to encourage them to convert office space to lab and R&D facilities as it seeks a larger life science influx.

“We want to make sure we have a link to those small startups that need to grow to Lexington,” Tintocalis said. “When you need to expand and need more square footage, it becomes cost-prohibitive in Kendall Square. When you have that second round of funding, a space out in Lexington is a little more affordable.”

Availabilities include Alexandria Real Estate Equities’ 29 Hartwell Ave., which has nearly 60,000 square feet of flex space available, said Jack Kerrigan, a principal for Avison Young.

In addition to existing vacancies, Cambridge-based King Street Properties is building a 91,000-square-foot spec building at 115 Hartwell Ave. marketed to life science tenants.

“East Cambridge is becoming home for Big Pharma and Big Tech, who are less rent-sensitive than traditional biotech companies,” said Bob Richards, president of Transwestern RBJ. “When you have vacancies under 3 percent in East Cambridge, it forces people to look at West Cambridge and Lexington or Waltham.”

All of the properties are attracting serious interest, said Duncan Gratton, an executive managing director for Cushman & Wakefield.

“I expect there will be in-migration to Lexington and possibly to Waltham from Cambridge,” Gratton said. “You’ll see some of the Cambridge effect in the Hartwell Avenue area. It’s not the rents pushing people out (of Cambridge), it’s just a lack of good properties.”

That would be a shift from recent years, in which absorption has been driven primarily by large office tenants such as Clarks N.A., Cympress, Wolverine Worldwide and TripAdvisor relocating or expanding within the central Route 128 submarket.

Many of the largest transactions were build-to-suit projects for large corporate users or updates of older buildings for tenants looking for flexible layouts and trendy amenities. The business plan continues to win favor among developers looking to compete with downtown office buildings at lower acquisition costs.

At 200 Smith St. in Waltham, Boston developer Anchor Line Partners and New York-based Northwood Investors paid $39.5 million in June for the 37-acre former U.S. Postal Service sorting facility. They’re planning to convert the 500,000-square-foot warehouse and offices into an amenities-rich workspace modeled upon The Reserve, an award-winning makeover of a 20-acre postal facility property in Los Angeles. The Waltham property is expected to be ready for occupancy in early 2017.

“It’ll be one-of-a-kind, unique Silicon Valley-style office space,” Avison Young’s Kerrigan said. “There’s very few large blocks of good existing office space available today.”

The largest current contiguous block of space is at Hobbs Brook Management’s 610 Lincoln St. in Waltham, which has 86,000 square feet available. The Waltham developer completed a $15 million gut rehab last year.

Boston Properties recently completed renovations of Reservoir Place North at 170 Tracer Lane in Waltham, a 75,000-square-foot, three-story office building. And Equity Industrial Properties is demolishing a single-story building at 2 Wells Ave. in Newton and building a 100,000-square-foot office building on speculation.

Central 128 Office Rents Approach Historic Highs

Tenants leased nearly 1 million square feet of office space during the fourth quarter in the Route 128/Mass Pike submarket, according to JLL data. The Route 128/Mass Pike submarket was the most active suburban region in Greater Boston during the fourth quarter of 2015 for office leasing.

Rents are approaching historic highs at trophy properties, as developers unveil the latest prototypes for creative office space in new and revamped buildings.

Boston Properties is quoting rents over $50 per square foot at its 245,000-square-foot 10 CityPoint complex in Waltham anchored by Wolverine Worldwide that opens this year, according to brokers.

That’s the highest price seen in the submarket since the recession, though well short of the record $70 per square foot that Bessemer Venture Partners paid for office space in Wellesley Hills in the previous decade.

Three smaller tenants are relocating from within Waltham after recently leasing a combined 48,500 square feet at 10 CityPoint: CYS Investments from Clarion Partners’ Waltham Woods, Infinidat from Boston Properties’ Waltham Weston Corporate Center and private equity firm J.W. Childs from Boston Properties’ Bay Colony Corporate Center.

“We’re close to all-time highs for suburban office rents,” Gratton said. “The 10 CityPoints are more than just suburban office. They’re got amenities in the building and in the neighborhood that were never there before. That’s a game-changer for the east side of 128 in Waltham.”