木脂素的生物合成及其微生物法生产的研究进展

doi:10.11949/0438-1157.20201089

摘要/Abstract

摘要：

木脂素是一类分布于植物中的次级代谢产物，由两分子苯丙素衍生物聚合而成。木脂素具有抗细菌、抗病毒和抗真菌活性，被广泛用于药物和食品中。目前，木脂素的生产主要依赖于植物提取。植物生长周期长、木脂素含量低等问题，限制了木脂素的商业应用。随着木脂素合成路径和关键酶的不断解析，木脂素的生物催化合成过程受到了越来越多的关注。本文总结了典型木脂素的生物活性、生物合成路径和微生物法生产的研究进展，可以为深入研究木脂素的微生物合成提供参考。

关键词: 木脂素, 合成生物学, 酶, 松脂素, 生物催化

Abstract:

Lignans are a class of secondary metabolites distributed in plants, which are formed by the polymerization of two molecules of phenylpropanine derivatives. Lignans have antibacterial, antiviral and antifungal activities, and are widely used in medicine and food. At present, lignans production mainly depends on plant extraction. The commercial application of lignans is limited by the problems of long plant growth period and low content. With the continuous demonstration of lignans biosynthesis pathways and key enzymes, biocatalytic synthesis of lignans has attracted more and more attention. In this review, the biological activity, biosynthesis pathway and microbial production of typical lignans were summarized, which may provide reference for the investigation of microbial synthesis of lignans.

Key words: lignans, synthetic biology, enzyme, pinoresinol, biocatalysis

中图分类号:

TQ 74

王炼, 吴迪, 周景文. 木脂素的生物合成及其微生物法生产的研究进展[J]. 化工学报, 2021, 72(1): 320-333.

WANG Lian, WU Di, ZHOU Jingwen. Research progress of lignans biosynthesis and their microbial production[J]. CIESC Journal, 2021, 72(1): 320-333.

图/表 6

图1 木脂素的基本骨架

Fig.1 Basic skeletons of lignans

图2 典型木脂素的结构

Fig.2 The structures of typical lignans

表1 木脂素的种类及其典型化合物的基本性质

Table 1 The categories of lignans and the basic characters of typical compounds

木脂素类别	典型化合物	天然来源	生物活性	其他合成方式
芳基萘	山荷叶素	丘生闭花木	治疗胃癌	无报道
芳基萘	赛菊芋黄素	台湾杉	抑制脑肿瘤转移	无报道
芳基四氢萘	鬼臼毒素	桃儿七、足叶草	抗肿瘤药物的前体	内生菌TW5
芳基四氢萘	南烛木树脂酚	小果南烛	皮肤美白剂	植物细胞培养
双并四氢呋喃	松脂素	木本植物、纤维植物	抗细菌和真菌、改善记忆障碍	植物细胞培养、微生物发酵
双并四氢呋喃	芝麻素	芝麻	抑制和阿尔兹海默症相关的部分症状	微生物发酵
二苄基丁内酯	罗汉松脂素	种子、蔬菜和水果	抗氧化、抗雌激素、抗骨质疏松	微生物发酵、化学合成
二苄基丁内酯	牛蒡酚	牛蒡	降低收缩血压	无报道
二苯并环辛二烯	五加前胡素	剑叶菊	未用于药物治疗	化学合成
二芳基丁烷	叶下珠脂素	叶下珠	抑制HepG2的增殖	无报道
二苄基丁酸乳酯	荜澄茄素	木材、根和树脂	镇痛、消炎	无报道
呋喃	落叶松脂素	菲律宾茜草	抗菌、抗氧化	微生物发酵

图3 植物松脂素合成途径松脂素、对香豆醇和咖啡醇的合成路径分别用红色、绿色和蓝色表示；PAL—苯丙氨酸解氨酶(phenylalanine ammonia-lyase)；C4H—肉桂酸-4-羟化酶(cinnamate 4-hydroxylase)；TAL—酪氨酸解氨酶(tyrosine ammonia-lyase)；C3H—香豆酸羟化酶(coumarate3-hydroxylase)；COMT—咖啡酸/5-羟基-阿魏酸 O-甲基转移酶(caffeic acid/5-hydroxy-ferulic acid O-methytransferase)；CCoAOMT—咖啡酰辅酶A 3-O-甲基转移酶(caffeoyl CoA 3-O-methyltransferase)；4CL—4-香豆酰辅酶A连接酶(4-hydroxycinnamate CoA ligase)；CCR—肉桂酰辅酶A还原酶(cinnamoyl CoA reductase)；CAD—肉桂醇脱氢酶(cinnamyl alcohol dehydrogenase)；DP—同化蛋白(dirigent protein)

Fig.3 The synthesis pathway of pinoresinol in plants

图4 芝麻素及其衍生物的天然合成路径CYP81Q1—胡椒醇/芝麻素合成酶；CYP92B14—细胞色素P450蛋白；UGT71A9，UGT94AA2，UGT94D1—尿苷糖基转移酶

Fig.4 The native biosynthesis of sesamin and derivatives

图5 亚麻木酚素和鬼臼毒素的生物合成路径PLR—松脂素/落叶松脂素还原酶(pinoresinol/lariciresinol reductase)；UGT74S1—尿苷糖基转移酶；SDH—开环异落叶松脂素脱氢酶(secoisolariciresinol dehydrogenase)

Fig.5 The biosynthetic pathway of secoisolariciresinol diglucoside and podophyllotoxin

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