神经酰胺类鞘脂的绿色生物制造

doi:10.12211/2096-8280.2024-059

摘要/Abstract

摘要：

神经酰胺是一种存在于所有真核生物中的多功能生物活性物质，在细胞信号转导、细胞增殖、分化、凋亡和免疫调节中发挥着重要作用。神经酰胺天然存在于皮肤角质层中，起着支持肌肤屏障、保持水分、抗氧化衰老、抗菌抗炎等作用。因此，神经酰胺及其衍生物在化妆品、生物医药、功能食品等领域具有广阔的市场前景。神经酰胺构型存在多个立体中心，化学从头合成难度大，已知市售的天然或类神经酰胺化合物主要是通过传统天然提取法及生物化学相结合的半合成法获得。近年来，利用微生物合成神经酰胺等鞘脂类化合物已有报道，但从头合成效率还处于较低水平，如何实现细胞工厂高效生产神经酰胺具有重大意义。本文从神经酰胺的生理功能和应用出发，系统地综述了神经酰胺类物质的生理效应及功能；阐述了神经酰胺的天然提取方法、神经酰胺及其前体化合物的化学合成方法；并从鞘脂合成途径及关键酶出发介绍，引出途径调控与优化、产物的运输储存与分泌、关键酶的挖掘与表达等改造策略；最后，从神经酰胺合成面临的聚集毒性、高效运输分泌、数字化改造催化元件、基因调控靶点的拓展等方面进行了展望。合成生物学和生物技术的持续进步有助于扩大微生物细胞工厂的生产能力，实现神经酰胺等鞘脂类化合物的可持续绿色生物制造。

关键词: 神经酰胺, 微生物细胞工厂, 生物合成, 鞘脂, 鞘氨醇碱

Abstract:

Ceramide, a fundamental bioactive molecule found ubiquitously in eukaryotic organisms, exerts profound regulatory effect on cellular physiology, encompassing critical roles in signaling cascades, cellular proliferation, differentiation, and apoptosis, as well as immunomodulation. In dermatology, ceramides play an indispensable role as constituents of the stratum corneum, the outermost layer of the skin, where they are crucial for maintaining the integrity of the epidermal barrier, regulating moisture retention, combating oxidative stress linked to aging, and exhibiting notable antimicrobial and anti-inflammatory properties. The multifaceted biological functions of ceramides underscore their extensive applications in various industries, including cosmetics, biomedicine, functional food, and animal nutrition, highlighting their significant market potential and therapeutic value. The chemical synthesis of ceramides poses substantial challenges due to the intricate stereochemistry involved, necessitating precise control over synthetic pathways. As a result, current commercial sources predominantly rely on semi-synthetic methods that integrate traditional natural extraction techniques with biochemical transformations of sphingolipid precursors to achieve targeted ceramide structures. Recent advancements in synthetic biology have explored microbial systems for the production of sphingolipids, including ceramides, offering promising avenues for scalable and sustainable synthesis. However, optimizing de novo synthesis pathways and their efficiency in microbial cell factories remains a primary research focus. Strategies aimed at enhancing ceramide yield and purity through metabolic engineering and pathway optimization are pivotal for advancing industrial applications. This paper provides a systematic review of the physiological effectiveness and function of ceramides, encompassing their physiological roles and various applications. It begins with an overview of ceramide extraction methods, including both natural extraction techniques and chemical synthesis approaches for ceramides and their precursor compounds. Subsequently, the review addresses the sphingolipid synthesis pathways and their associated key enzymes, detailing strategies for pathway regulation and optimization, as well as the aspects of product transport, storage, and secretion. Additionally, it explores the identification and expression of key enzymes. The paper concludes by examining future directions in the field, such as addressing aggregation toxicity in ceramide synthesis, enhancing transport and secretion mechanisms, advancing digital modifications of catalytic elements, and expanding gene regulatory target exploration. By synthesizing current knowledge and highlighting avenues for innovation, this review aims to catalyze further research effort toward achieving efficient ceramide production. Ultimately, optimizing ceramide synthesis has the potential to unlock its full potential in various sectors, contributing to its advancement in skincare, therapeutics, and functional materials. The integration of microbial systems is particularly promising for expanding production capabilities while addressing sustainability concerns in ceramide manufacturing. Continued advancements in synthetic biology and biotechnology are expected to revolutionize the landscape of ceramide applications, paving the way for enhanced therapeutic interventions and novel industrial applications in the future.

Key words: ceramide, microbial cell factories, biosynthesis, sphingolipids, sphingosine alkali

中图分类号:

Q819

鲁锦畅, 武耀康, 吕雪芹, 刘龙, 陈坚, 刘延峰. 神经酰胺类鞘脂的绿色生物制造[J]. 合成生物学, 2025, 6(2): 422-444.

LU Jinchang, WU Yaokang, LV Xueqin, LIU Long, CHEN Jian, LIU Yanfeng. Green biomanufacturing of ceramide sphingolipids[J]. Synthetic Biology Journal, 2025, 6(2): 422-444.

图/表 10

图1 皮肤中神经酰胺结构和命名

Fig. 1 Structures and nomenclatures of cutaneous ceramides

图2 神经酰胺生产方法

Fig. 2 Production methods of ceramides

表1 神经酰胺及前体鞘氨醇碱的化学合成法

Table 1 Chemical synthesis of ceramides and their precursor sphingosine base

	出发底物	产物	总收率	参考文献
鞘氨醇碱从头合成	2-叠氮-4-硝基苯基磺酸衍生物	鞘氨醇；植物鞘氨醇	58%	[33]
	立体选择性的环氧化物	鞘氨醇	51%	[34]
	D-葡萄糖衍生物	D-赤式鞘氨醇； D-苏式鞘氨醇	52%	[35]
	L-丝氨酸	鞘氨醇；鞘磷脂；1-磷酸鞘氨醇；鞘氨醇衍生物	37%	[36]
	N-Boc-L-丝氨酸	鞘氨醇	71%	[37]
神经酰胺从头合成	三羟甲基氨基甲烷；脂肪酸羟基取代物	神经酰胺类似物	33%～65%	[38]
	（2S）-2-氨基苯乙醇（苯甘氨醇）；（1R,2R）2-氨基-1-苯基-1,3-丙二醇；（S）-2-氨基（-4-甲氧基）苯乙醇	神经酰胺类似物	63.5%	[39]
	羟化脂肪酸；环氧甘油基醚	神经酰胺类似物	60%～75%	[40]
	N-十六烷基-2-氨基乙醇；环己烷；丙二酸二甲酯	神经酰胺类似物	69%	[41]
	C₁₆-烷基烯二聚体；二乙醇胺/N-甲基-2,3,4,5,6-五羟基己胺/D-氨基葡萄糖/3-氨基-1,2-丙二醇/N-（1,3-二羟基异丙基）胺/N-（2,3,4,5,6-五羟基己基）胺等	神经酰胺类似物	20%～90%	[42-43]
脂肪酸与鞘碱化学法合成神经酰胺	神经鞘氨醇；不同碳链长度有机酸	神经酰胺类似物	51%～96%	[21]
	共轭羧酸与N‑羟基琥珀酰亚胺；鞘氨醇	含共轭羧酸的神经酰胺	50%～70%	[44]
	羧酸；植物鞘氨醇	神经酰胺Ⅲ	84％	[45]
脂肪酸与鞘碱生物酶法法合成神经酰胺	二氢鞘氨醇；脂肪酸；Novozym 435	神经酰胺NG	70%～98%	[46]
	活化的羧酸衍生物；植物鞘氨醇/二氢鞘氨醇；Novozym 435	神经酰胺	98%～99.7%	[47]
	植物鞘氨酸；脂肪酸；Novozym 435	神经酰胺Ⅲ	94%	[48]

表2 神经酰胺及前体衍生物的生物合成法

Table 2 Biosynthesis of ceramides and their precursor derivatives

宿主	产物	底物碳源	策略	产量	参考文献
威克汉姆西弗酵母	三乙酰鞘氨醇	葡萄糖	异源表达棉桃阿舒来源laf1和des1；突变SYR、DES	33.45 mg/g DCW （500 mL挡板摇瓶）	[56]
威克汉姆西弗酵母（P.ciferrii lig4D strain CS.PCDPro2）	四乙酰植物鞘氨醇	33 g/L葡萄糖	阻断shm1、shm2；缺失cha1；删除lcb4；过表达lcb1、lcb2；敲除orm1、orm2；过表达sur2	199 mg/g DCW；2 g/L （摇瓶培养）	[57]
威克汉姆西弗酵母（NRRL Y1031）	四乙酰植物鞘氨醇	33 g/L葡萄糖	—	（291.2±63.7） mg/L （120 mL/500 mL挡板摇瓶）	[58]
威克汉姆西弗酵母 NRRL Y-1031（M40）	四乙酰植物鞘氨醇	30 g/L葡萄糖 30g /L糖蜜	EMS诱变；BODIPY 505/515染色；荧光激活细胞分选（FACS）	2.895 g/L （5.6 L生物反应器）	[59]
酿酒酵母K26	二乙酰植物鞘氨醇	33 g/L葡萄糖	质粒表达异源基因sli1、atf2	（4.3±0.8） mg/L （120 mL/500 mL挡板摇瓶）	[58]
酿酒酵母K26	三乙酰植物鞘氨醇	33 g/L葡萄糖	质粒表达异源基因sli1、atf2	（1.2±0.1） mg/L （120 mL/500 mL挡板摇瓶）	[58]
解脂耶氏酵母PO1g（MatA, leu2-270, ura3-302::URA3, xpr2-332. axp-2）	四乙酰植物鞘氨醇	200 g/L甘油橄榄油	异源表达sli1、atf2；删除lcb4基因；有性杂交；发酵优化	（650±24） mg/L （5 L生物反应器）	[60]
威克汉姆西弗酵母 F-60-10A NRRL1031 诱变后菌株：Mutant736	四乙酰植物鞘氨醇	5 g/L丝氨酸； 50 g/L甘油；补加甘油	γ射线诱变	17.7 g/L （3 L生物反应器）	[61]
威克汉姆西弗酵母	四乙酰植物鞘氨醇	50 g/L甘油； 5 g/L L‑丝氨酸	ARTP诱变	30.47 g/L （5 L生物反应器）	[62]
威克汉姆西弗酵母DSCC 7-25 （KCCM-10131）	四乙酰植物鞘氨醇	25~35 g/L甘油	从NRRL Y-1031单倍体分离	14 g/L （500 L生物反应器）	[63]
威克汉姆西弗酵母CGMCC19562	四乙酰植物鞘氨醇	6.0 g/L L‑丝氨酸； 42.0 g/L甘油	单倍体分离	22.14 g/L （生物反应器）	[64]
酿酒酵母 CEN.PK2‑1D	植物鞘氨醇	500 g/L葡萄糖	敲除lcb4、shm2、cha1；orm2:: tsc10；elo3::sur2；shm1::lcb1,lcb2； delta 22::hac1	2817 mg/L；150.54 mg/g干重（5 L生物反应器）	[65]
酿酒酵母NCYC 3608（MATalpha gal2 ho::HygMX ura3::KanMX）	植物鞘氨醇	20 g/L葡萄糖	缺失his3、leu2、ura3、cha1、cha2、lcb4、lcb5、orm2；质粒过表达ARS/CEN/URA/ScTSC10/ScSUR2、ARS/CEN/HIS/ScLCB1/ScLCB2、ARS/CEN/LEU	2169 mg/L	[66]
酿酒酵母KCCM50515	神经酰胺	20 g/L葡萄糖	发酵优化	1.46 mg/L	[67]
酿酒酵母 KCCM 50515（Matα ura3-52 lys2-801 ade2-101 trp1-∆63 his3-∆200 leu2-∆1）	神经酰胺	20 g/L葡萄糖	过表达tscl0	9.8 mg/g cell	[68]
酿酒酵母	神经酰胺	葡萄糖；半乳糖	过表达tsc10	10.52 mg/g cell	[69]
酿酒酵母 SCEL2,1	神经酰胺	葡萄糖；半乳糖	过表达lcb1、lcb2	10.08 mg /g cell	[69]
酿酒酵母 SCEG1C1	神经酰胺	葡萄糖；半乳糖	过表达lag1、lac1	9.88 mg/g cell	[69]
酿酒酵母	神经酰胺NS	葡萄糖	敲除sur2和scs7；引入人类鞘脂去饱和酶基因des1；失活ydc1；过表达isc1；des1基因产物的内质网定位	未定量	[70]
巴斯德毕赤酵母GS115	神经酰胺（d18:0）	10 g/L甘油	敲除Ku70同源的基因 PAS_chr3_0329；敲除orm1、orm2 同系物同源基因 PAS_chr4_0427	90.22 mg/L	[71]

表2 神经酰胺及前体衍生物的生物合成法

Table 2 Biosynthesis of ceramides and their precursor derivatives

宿主	产物	底物碳源	策略	产量	参考文献
威克汉姆西弗酵母	三乙酰鞘氨醇	葡萄糖	异源表达棉桃阿舒来源laf1和des1；突变SYR、DES	33.45 mg/g DCW （500 mL挡板摇瓶）	[56]
威克汉姆西弗酵母（P.ciferrii lig4D strain CS.PCDPro2）	四乙酰植物鞘氨醇	33 g/L葡萄糖	阻断shm1、shm2；缺失cha1；删除lcb4；过表达lcb1、lcb2；敲除orm1、orm2；过表达sur2	199 mg/g DCW；2 g/L （摇瓶培养）	[57]
威克汉姆西弗酵母（NRRL Y1031）	四乙酰植物鞘氨醇	33 g/L葡萄糖	—	（291.2±63.7） mg/L （120 mL/500 mL挡板摇瓶）	[58]
威克汉姆西弗酵母 NRRL Y-1031（M40）	四乙酰植物鞘氨醇	30 g/L葡萄糖 30g /L糖蜜	EMS诱变；BODIPY 505/515染色；荧光激活细胞分选（FACS）	2.895 g/L （5.6 L生物反应器）	[59]
酿酒酵母K26	二乙酰植物鞘氨醇	33 g/L葡萄糖	质粒表达异源基因sli1、atf2	（4.3±0.8） mg/L （120 mL/500 mL挡板摇瓶）	[58]
酿酒酵母K26	三乙酰植物鞘氨醇	33 g/L葡萄糖	质粒表达异源基因sli1、atf2	（1.2±0.1） mg/L （120 mL/500 mL挡板摇瓶）	[58]
解脂耶氏酵母PO1g（MatA, leu2-270, ura3-302::URA3, xpr2-332. axp-2）	四乙酰植物鞘氨醇	200 g/L甘油橄榄油	异源表达sli1、atf2；删除lcb4基因；有性杂交；发酵优化	（650±24） mg/L （5 L生物反应器）	[60]
威克汉姆西弗酵母 F-60-10A NRRL1031 诱变后菌株：Mutant736	四乙酰植物鞘氨醇	5 g/L丝氨酸； 50 g/L甘油；补加甘油	γ射线诱变	17.7 g/L （3 L生物反应器）	[61]
威克汉姆西弗酵母	四乙酰植物鞘氨醇	50 g/L甘油； 5 g/L L‑丝氨酸	ARTP诱变	30.47 g/L （5 L生物反应器）	[62]
威克汉姆西弗酵母DSCC 7-25 （KCCM-10131）	四乙酰植物鞘氨醇	25~35 g/L甘油	从NRRL Y-1031单倍体分离	14 g/L （500 L生物反应器）	[63]
威克汉姆西弗酵母CGMCC19562	四乙酰植物鞘氨醇	6.0 g/L L‑丝氨酸； 42.0 g/L甘油	单倍体分离	22.14 g/L （生物反应器）	[64]
酿酒酵母 CEN.PK2‑1D	植物鞘氨醇	500 g/L葡萄糖	敲除lcb4、shm2、cha1；orm2:: tsc10；elo3::sur2；shm1::lcb1,lcb2； delta 22::hac1	2817 mg/L；150.54 mg/g干重（5 L生物反应器）	[65]
酿酒酵母NCYC 3608（MATalpha gal2 ho::HygMX ura3::KanMX）	植物鞘氨醇	20 g/L葡萄糖	缺失his3、leu2、ura3、cha1、cha2、lcb4、lcb5、orm2；质粒过表达ARS/CEN/URA/ScTSC10/ScSUR2、ARS/CEN/HIS/ScLCB1/ScLCB2、ARS/CEN/LEU	2169 mg/L	[66]
酿酒酵母KCCM50515	神经酰胺	20 g/L葡萄糖	发酵优化	1.46 mg/L	[67]
酿酒酵母 KCCM 50515（Matα ura3-52 lys2-801 ade2-101 trp1-∆63 his3-∆200 leu2-∆1）	神经酰胺	20 g/L葡萄糖	过表达tscl0	9.8 mg/g cell	[68]
酿酒酵母	神经酰胺	葡萄糖；半乳糖	过表达tsc10	10.52 mg/g cell	[69]
酿酒酵母 SCEL2,1	神经酰胺	葡萄糖；半乳糖	过表达lcb1、lcb2	10.08 mg /g cell	[69]
酿酒酵母 SCEG1C1	神经酰胺	葡萄糖；半乳糖	过表达lag1、lac1	9.88 mg/g cell	[69]
酿酒酵母	神经酰胺NS	葡萄糖	敲除sur2和scs7；引入人类鞘脂去饱和酶基因des1；失活ydc1；过表达isc1；des1基因产物的内质网定位	未定量	[70]
巴斯德毕赤酵母GS115	神经酰胺（d18:0）	10 g/L甘油	敲除Ku70同源的基因 PAS_chr3_0329；敲除orm1、orm2 同系物同源基因 PAS_chr4_0427	90.22 mg/L	[71]

图3 酵母鞘脂代谢通路（绿色代表编码基因，红色代表酶。3-P-Glycerate—3磷酸甘油酸；Palmitoy CoA—棕榈酰辅酶A；5，10-THF—5，10-二甲基四氢叶酸；L-Glycine—L-甘氨酸；3-KDS—3-酮基-二氢鞘氨醇；DHS—二氢鞘氨醇；PHS—植物鞘氨醇；S—鞘氨醇；1-P-DHS—1-磷酸二氢鞘氨醇；1-P-PHS—1-磷酸植物鞘氨醇；P-Etn—磷酸乙醇胺；Pi—磷酸基团；IPC—肌醇磷酸神经酰胺；GDP-Man—鸟苷二磷酸甘露糖；MIPC—甘露糖肌醇磷酸神经酰胺；M（IP）2C—甘露糖-（肌醇-P）2-神经酰胺； GlcCer—葡萄糖糖神经酰胺； SM—鞘磷脂；C1P—神经酰胺1-磷酸盐；ser1—3-磷酸丝氨酸氨基转移酶编码基因；ser2—磷酸甘油酸途径的磷酸丝氨酸磷酸酶编码基因；ser3—3-磷酸甘油酸脱氢酶编码基因；shm1，shm2—L-丝氨酸羟甲基转移酶编码基因；cha1—L-丝氨酸脱氨酶编码基因；lcb1、lcb2、tsc3—丝氨酸棕榈酰转移酶编码基因；tsc10—3-酮基-二氢鞘氨醇还原酶编码基因；des1—鞘脂Δ4-去饱和酶编码基因；lcb4，lcb5—鞘氨醇激酶编码基因；dpl1—鞘碱磷酸裂解酶编码基因；sur2—C4 羟化酶编码基因；lag1，lac1，lip1—神经酰胺合成酶编码基因；aur1—神经酰胺磷酸肌醇转移酶编码基因；csg1，csg2，csh1，sur1—甘露糖基肌醇磷酸神经酰胺合酶催编码基因；ipt1—肌醇磷酸转移酶编码基因；isc1—复杂鞘脂头基水解酶编码基因；ypc1、ydc1—碱性神经酰胺酶编码基因；ORM1，ORM2—介导鞘脂稳态蛋白；SPT—丝氨酸棕榈酰转移酶；KDSR—3-酮基-二氢鞘氨醇还原酶；CerS—神经酰胺合酶；CERT—神经酰胺转运蛋白； SMS—鞘磷脂合成酶；SMase—鞘磷脂酶家族；CK—经酰胺激酶；ER—内质网）

Fig. 3 Metabolic pathway of sphingolipid in yeast(Green represents the coding gene, red represents the enzyme. 5,10-THF—5,10-dimethyltetrahydrofolate; 3-KDS—3-keto-dihydrosphingosine; DHS—dihydrosphingosine; PHS—phytosphingosine; S—S phingosine; 1-P-DHS—dihydrosphingosine-1-phosphate; 1-P-PHS—phytosphingosine-1-phosphate; P-Etn—phosphoryl ethanolamine; Pi—phosphate group; IPC—inositol phosphorylceramide; GDP-Man—GDP mannose; MIPC—mannosyl-inositol phosphorylceramide; M(IP)2C—mannosyl-diinositol phosphorylceramide; GlcCer—glucosylceramide; SM—sphingomyelin; C1P—ceramide-1phosphate; ser1—3-phosphoserine aminotransferase encoding gene; ser2—phosphoserine phosphatase in the phosphoglycerate pathway encoding gene; ser3—3-phosphoglycerate dehydrogenase encoding gene; shm1, shm2—L-serine hydroxymethyltransferase encoding gene; cha1—L-serine deaminase encoding gene; lcb1, lcb2, tsc3—serine palmitoyltransferase encoding gene; tsc10—3-keto-dihydrosphingosine reductase encoding gene; des1—sphingolipid Δ4-desaturase encoding gene; lcb4, lcb5—sphingosine kinase encoding gene; dpl1—sphingobase-1-phosphate lyase encoding gene; sur2—C4 hydroxylase encoding gene; lag1, lac1, lip1—ceramide synthase encoding gene; aur1—ceramide phosphoinositide transferase encoding gene; csg1, csg2, csh1, sur1—mannosylinositol phosphorylceramide synthase encoding gene; ipt1—inositol phosphotransferase encoding gene; isc1—complex sphingolipid headgroup hydrolase encoding gene; ypc1, ydc1—alkaline ceramidase encoding gene; ORM1, ORM2—mediate sphingolipid homeostasis protein; SPT—serine palmitoyl transferase; KDSR—3-ketodihydrosphingosine reductase; CerS—ceramide synthase; CERT—ceramide transfer protein; SMS—sphingomyelin synthase; SMase—sphingomyelinase; CK—ceramide kinase; ER—endoplasmic reticulum)

图4 丝氨酸棕榈酰转移酶催化合成3-KDS简图（SPT—丝氨酸棕榈酰转移酶；ORM—调节鞘脂稳态蛋白；3-KDS—3-酮基-二氢鞘氨醇；TM—跨膜区；LCB1，LCB2，TSC3—丝氨酸棕榈酰转移酶亚基；ER—内质网）

Fig. 4 Schematic diagram for the catalytic synthesis of 3-KDS by serine palmitoyl transferase(SPT—serine palmitoyl transferase; ORM—mediate sphingolipid homeostasis protein;3-KDS—3-keto-dihydrosphingosine; TM—Transmembrane; LCB1, LCB2, TSC3—subunits of serine palmitoyltransferase; ER—endoplasmic reticulum)

图5 3-酮二氢鞘氨醇还原酶催化合成DHS简图（3-KDS—3-酮基-二氢鞘氨醇；KDSR—3-酮基-二氢鞘氨醇还原酶；DHS—二氢鞘氨醇；ER—内质网）

Fig. 5 Schematic diagram for the catalytic synthesis of DHS by 3-ketodihydrosphingosine reductase(3-KDS—3-keto-dihydrosphingosine; KDSR—3-keto-dihydrosphingosine reductase; TSC10—3-keto-dihydrosphingosine reductase; DHS—dihydrosphingosine; ER—endoplasmic reticulum)

图6 神经酰胺合酶催化合成神经酰胺简图（LCB—长链鞘氨醇碱；FA—脂肪酸；CerS—神经酰胺合酶；Cer—神经酰胺；LAG1，LAC1，LIP1—神经酰胺合成酶亚基；ER—内质网）

Fig. 6 Schematic diagram for the catalytic synthesis of ceramide by ceramide synthase(LCB—long chain sphingosine bases; FA—fatty acid; CerS—ceramide synthase; Cer—ceramide; LAG1, LAC1, LIP1—subunits of ceramide synthase; ER—endoplasmic reticulum)

图7 神经酰胺生物合成途径改造策略（3-KDS—3-酮基-二氢鞘氨醇；ORM—介导鞘脂稳态蛋白； SPT—丝氨酸棕榈酰转移酶；DHS—二氢鞘氨醇；PHS—植物鞘氨醇；Cer—神经酰胺；GlcCer—葡萄糖糖神经酰胺；SM—鞘磷脂；CerS—神经酰胺合酶）

Fig. 7 Strategy for the modification of the ceramide biosynthetic pathway(3-KDS—3-keto-dihydrosphingosine; ORM—mediate sphingolipid homeostasis protein; SPT—serine palmitoyl transferase; DHS—dihydrosphingosine; PHS—phytosphingosine; Cer—ceramide; GlcCer—glucosylceramide; SM—sphingomyelin; CerS—ceramide synthase)

图8 DES1、SLI1、ATF2催化合成神经酰胺示意图（CerS—神经酰胺合酶；des1—人鞘脂去饱和酶编码基因；WcSli1，WcAtf2—威克汉姆西弗酵母鞘碱N/O-乙酰转移酶编码基因）

Fig. 8 Diagram for the catalytic synthesis of ceramides by DES1、SLI1 and ATF2(CerS—Ceramide synthase; des1—Human sphingolipid desaturase encoding gene; WcSli1, WcAtf2—Wickhamomyces ciferrii sphingobase N/O-acetyltransferase encoding genes)

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