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Efficient acetoin production from pyruvate by engineered whole-cell biocatalysis

《化学科学与工程前沿（英文）》 2023年第17卷第4期页码 425-436 doi: 10.1007/s11705-022-2229-0

摘要： Acetoin is an important platform chemical, which has a wide range of applications in many industries. Halomonas bluephagenesis, a chassis for next generation of industrial biotechnology, has advantages of fast growth and high tolerance to organic acid salts and alkaline environment. Here, α-acetolactate synthase and α-acetolactate decarboxylase from Bacillus subtilis 168 were co-expressed in H. bluephagenesis to produce acetoin from pyruvate. After reaction condition optimization and further increase of α-acetolactate decarboxylase expression, acetoin production and yield were significantly enhanced to 223.4 mmol·L^–1 and 0.491 mol·mol^–1 from 125.4 mmol·L^–1 and 0.333 mol·mol^–1, respectively. Finally, the highest titer of 974.3 mmol·L^–1 (85.84 g·L^–1) of acetoin was accumulated from 2143.4 mmol·L^–1 (188.6 g·L^–1) of pyruvic acid within 8 h in fed-batch bioconversion under optimal reaction conditions. Moreover, the reusability of the cell catalysis was also tested, and the result illustrated that the whole-cell catalysis obtained 433.3, 440.2, 379.0, 442.8 and 339.4 mmol·L^–1 (38.2, 38.8, 33.4, 39.0 and 29.9 g·L^–1) acetoin in five repeated cycles under the same conditions. This work therefore provided an efficient H. bluephagenesis whole-cell catalysis with a broad development prospect in biosynthesis of acetoin.

关键词： acetoin pyruvate α-acetolactate synthetase α-acetolactate decarboxylase Halomonas bluephagenesis whole-cell biocatalysis

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HERBICIDES THAT INHIBIT ACETOLACTATE SYNTHASE

《农业科学与工程前沿（英文）》 2022年第9卷第1期页码 155-160 doi: 10.15302/J-FASE-2021420

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ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/-catenin signaling by palmitoylation modification

《医学前沿（英文）》 2023年第17卷第4期页码 685-698 doi: 10.1007/s11684-022-0942-1

摘要： Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

关键词： acute myeloid leukemia acyl-CoA synthetase long chain family member 5 Wnt3a palmitoylation ABT-199