Biosynthesis of 3-hydroxypropionate, an important platform chemical

3-Hydroxypropionate (3HP) is one of the top 12 value-added chemicals from biomass released by the US Department of Energy, serving as a precursor to a variety of commodity chemicals like acrylate and acrylamide, as well as a monomer of biodegradable plastic. To establish a sustainable way to produce these commercially important chemicals and materials, fermentative production of 3HP was thoroughly investigated in our lab in recent years. Firstly, a novel 3HP biosynthetic pathway employing malonyl-CoA as an intermediate was developed. Compared with other 3HP pathways, the malonylCoA route have some expected advantages, including broad raw material spectrum, redox neutral, and free of cofactor. Secondly, the 3HP productivity via malonyl-CoA pathway was significantly improved by dissection of malonyl-CoA reductase (MCR, the key enzyme converting malonyl-CoA into 3HP) into two functional fragments, directed evolution of rate-limiting fragment MCR-C, carbon flux balancing and redirection toward 3HP biosynthesis. The 3HP production increased from 0.1 g/L to 40.6 g/L, about 50 times higher than that in previous report. Furthermore, a series of 3HPcontaining copolymers with fully controllable structures was directly synthesized using inexpensive carbon sources as glucose and glycerol, differing from previously reported approaches based on addition of precursors. The thermal and mechanical properties of copolymers dramatically changed depending on their structure and monomer ratios, which should widen their range of applications. Our study not only set up the sustainable route for production 3HP and its polymers, but also established some new methods for metabolic engineering, such as protein dissection and carbon flux redirection, which can be used in biosynthesis of other promising chemicals and materials.