Totally atom-economical synthesis of lactic acid from formaldehyde: combined bio-carboligation and chemo-rearrangement without the isolation of intermediates

Abstract

Non-fermentative chemoenzymatic transformations have attracted great interest of both academia and industry. Here, we report a green chemoenzymatic cascade reaction that converts the C1 compound formaldehyde into lactic acid using...

Development of a kinetic model and figures of merit for formaldehyde carboligations catalyzed by formolase enzymes

“…capable of describing linear (Siegel et al, 2015), Michaelis-Menten (Güner et al, 2021), and sigmoidal (Cai et al, 2021;T. Li et al, 2020) velocity curves without invoking unnecessary empirical kinetic models.…”

“…In an alternative approach, benzoylformate decarboxylase was also used as a template to design a glycolaldehyde synthase (GALS), a synthetic formolase-like enzyme with GALD as its primary product (Lu et al, 2019). Several variants based on GALS have been designed recently as well (T. Li et al, 2020).…”

One-pot chemoenzymatic synthesis of glycolic acid from formaldehyde

“…For the first bio-carboligation step in this chemoenzymatic cascade reaction, a formolase (BFD-M4: W86R/N87T/L109G/ L110E/A460M/H281Y) 9 was further engineered to efficiently catalyze the carboligation of formaldehyde through two rounds of directed evolution (∼4000 clones). Both GA and DHA were detected using a color reaction for epPCR library screening.…”

“…DHA is an important C3 platform chemical, 8 which has been produced from the C1 compound formaldehyde in our previous work. 9 C1 compounds, including CO 2 , CO, CH 4 , HCOOH, CH 3 OH and HCHO, are attractive renewable resources for both the chemical and biotechnology industries due to their abundance, low-cost and convenient production. 10 The utilization of C1 compounds as raw materials is a new trend in the field of biological manufacturing and is crucial for establishing a sustainable circular carbon economy.…”

“…Firstly, oxidants have been screened for the conversion of GA and DHA to glycolic acid, which is the second step in the chemoenzymatic cascade reaction. Since the formolase-catalyzed carboligation of formaldehyde produces both a C2 aldehyde (GA) and C3 ketone (DHA), 9,14 it is desirable to convert both GA and DHA using the same oxidant by our designed chemoenzymatic pathway. According to the literature, DHA was oxidized to glycolate and formate in the presence of H 2 O 2 and NH 4 OH, 15 and GA was converted into glycolic acid by chlorite in the presence of a mixture of DMSO and phosphate buffer (pH 4).…”