Reprogramming glycolysis for directing glycolytic metabolites to a specific metabolic pathway is expected to be useful for increasing microbial production of certain metabolites, such as amino acids, lipids or considerable secondary metabolites. In this report, a strategy of increasing glycolysis by altering the metabolism of inositol pyrophosphates (IPs) for improving the production of S-adenosyl-l-methionine (SAM) for diverse pharmaceutical applications in yeast is presented. The genes associated with the metabolism of IPs, arg82, ipk1 and kcs1, were deleted, respectively, in the yeast strain Saccharomyces cerevisiae CGMCC 2842. It was observed that the deletions of kcs1 and arg82 increased SAM by 83.3 % and 31.8 %, respectively, compared to that of the control. In addition to the improved transcription levels of various glycolytic genes and activities of the relative enzymes, the levels of glycolytic intermediates and ATP were also enhanced. To further confirm the feasibility, the kcs1 was deleted in the high SAM-producing strain Ymls1ΔGAPmK which was deleted malate synthase gene mls1 and co-expressed the Acetyl-CoA synthase gene acs2 and the SAM synthase gene metK1 from Leishmania infantum, to obtain the recombinant strain Ymls1Δkcs1ΔGAPmK. The level of SAM in Ymls1Δkcs1ΔGAPmK reached 2.89 g L⁻¹ in a 250-mL flask and 8.86 g L⁻¹ in a 10-L fermentation tank, increasing 30.2 % and 46.2 %, respectively, compared to those levels in Ymls1ΔGAPmK. The strategy of increasing glycolysis by deletion of kcs1 and arg82 improved SAM production in yeast.

重新编程糖酵解以将糖酵解代谢物引导至特定的代谢途径，有望用于增加某些代谢物（例如氨基酸，脂质或大量次级代谢物）的微生物产生。在该报告中，提出了通过改变肌醇焦磷酸盐（IPs）的代谢来增加糖酵解的策略，以改善酵母中各种药物应用的S-腺苷-1-甲硫氨酸（SAM）的产量。在酵母菌株Saccharomyces cerevisiae CGMCC 2842中，分别缺失了与IPs代谢相关的基因arg82，ipk1和kcs1。观察到kcs1和kcs1的缺失。与对照相比，arg82分别使SAM增加了83.3％和31.8％。除了改善了各种糖酵解基因的转录水平和相关酶的活性外，糖酵解中间体和ATP的水平也得到了提高。为了进一步证实可行性，所述kcs1是在高SAM生产菌株ý删除MLS1 ΔGAPmK其中已删除苹果酸合酶基因MLS1和共表达的乙酰-CoA合酶基因ACS2和SAM合成酶基因metK1从婴儿利什曼原虫，以获得重组菌株Y MLS1 Δ kcs1 ΔGAPmK。SAM的水平，以Y mls1为单位Δ kcs1 ΔGAPmK达到2.89克L- ^-1在250ml的烧瓶中，8.86克L- ^-1在10-L发酵罐，增加分别为30.2％和46.2％，相比于沿Y那些水平MLS1 ΔGAPmK。通过删除kcs1和arg82来增加糖酵解的策略改善了酵母中SAM的产生。