BMC Biology:中科院武汉植物园章焰生研究组发表抗癌原料药白桦脂

2016年8月17日，国际学术BMC系列旗舰刊物《BMC biology》杂志上在线发表了中国科学院武汉植物园天然药物生物合成课题组章焰生研究员的一篇研究论文，论文报道了在抗癌原料药白桦脂酸生物合成方面取得新进展。硕士研究生周晨为论文第一作者，章焰生研究员为论文通讯作者。

白桦脂酸为五环三萜类化合物，该化合物本身以及其衍生物对多种人类癌症疾病具有较好的治疗功效，尤其是对结肠癌以及黑色瘤的抑制作用明显。白桦脂酸在很多种植物中均有合成，但其主要来源为白桦树的树皮，含量约为万分之几数量级。

据中国国家统计局数据显示，中国目前每年需求白桦脂酸的量在18-20吨左右，消耗约23万吨的白桦树树皮用以提取制备白桦脂酸，随着药物市场需求的迅猛增长，以及白桦树资源的有限性，白桦脂酸供应链出现断层现象，中国多家生产白桦脂酸的公司也因此而停产白桦脂酸，从而造成了白桦脂酸市场供应与需求之间的巨大脱节。

研究人员利用白桦树的树皮为研究材料，从中分离了控制白桦脂酸合成的关键细胞色素氧化酶基因，被命名为BPLO基因。BPLO较之前发表的来源于其它几种植物的细胞色素氧化酶，展现了明显较高的催化白桦脂酸合成活性;利用BPLO基因，本组进一步在微生物酵母细胞中人工重建了白桦脂酸生物合成途径，构建的酵母工程菌利用常用培养基即能合成植物来源化合物白桦脂酸;在此基础之上，该研究组还尝试比较了不同种酵母承载白桦脂酸的合成能力，发现酵母自身的遗传差异对白桦脂酸合成具有较大的影响。

原文链接：

Improvement of betulinic acid biosynthesis in yeast employing multiple strategies.

原文摘要：

BACKGROUND:Betulinic acid (BA) is a lupane-type triterpene which has been considered as a promising agent to cure melanoma with no side effects. Considering that BA is naturally produced in small quantities in plants, we previously reported the success in engineering its production in yeast. In the present study, we attempted to improve BA biosynthesis in yeast by the use of different strategies.

RESULTS:We first isolated a GENE encoding a lupeol C-28 oxidase (LO) from Betula platyphylla (designated as BPLO). BPLO showed a higher activity in BA biosynthesis compared to the previously reported LOs. In addition, two yeast platforms were compared for engineering the production of BA, which demonstrated that the WAT11 strain was better to host BA pathway than the CEN.PK strain. Based on the WAT11-chassiss, the Gal80p mutant was further constructed. The mutant produced 0.16 mg/L/OD600 of BA, which was 2.2 fold of that produced by the wild type strain (0.07 mg/L/OD600).

CONCLUSIONS:This study reported our efforts to improve BA production in yeast employing multiple strategies, which included the identification of a novel LO enzyme with a higher activity in BA biosynthesis, the evaluation of two yeast strains for hosting the BA pathway, and the up-regulation of the expression of the BA pathway genes by managing yeast GAL gene regulon circuit.

doi: 10.1186/s12896-016-0290-9

作者：章焰生