Research progress in biosynthesis of podophyllotoxin and its derivatives / 生物工程学报

Podophyllotoxin (PTOX) is an aryl-tetralin lignan of plant origin found in some species of Podophyllum such as Dysosma versipellis, Diphylleia sinensis, and Sinopodophyllum hexandrum. Etoposide and teniposide are produced semisynthetically from PTOX and used clinically to treat several forms of cancer. As a typical representative of new drug discovery from natural products, the production of PTOX solely depends on extraction from plants, resulting in severe contradiction between supply and demand. With the advantages of unconstrained resources and eco-friendly reaction conditions, biosynthesis method has become a trend in the production of PTOX and its derivatives. In this review, we summarize the research progress of PTOX biosynthesis in plants and expound the functions of the key enzymes as well as their subcellular location. The synthetic biology for production of PTOX intermediates in a tobacco chassis is also introduced. Finally, the heterologous expression and biotransformation of PTOX in microorganisms is summarized, which sets the foundation for the efficient microbial production of PTOX using cell factories.

Efficacy of Extended Myectomy on Reducing Mitral Regurgitation in Patients With Hypertrophic Obstructive Cardiomyopathy / 中国循环杂志

Objectives:To analyze the impact of extended myectomy on reducing mitral regurgitation in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods:We retrospectively analyzed 480 consecutive HOCM patients who underwent surgical treatment by the same surgeon in our institution from October 2002 to July 2017. The efficacy of extended myectomy for reducing mitral regurgitation and left ventricular outflow tract (LVOT) obstruction were evaluated by echocardiography after surgery. Results:Among the 480 patients, 22 (4.6%) received concomitant mitral repair or replacement because of their intrinsic mitral diseases. In the remaining 458 (95.4%) patients without concomitant mitral valve surgery, 1 (0.2%) died at the 5th day after surgery because of infective shock, and another 4 (0.9%) lost to follow-up, a total of 453 (98.9%) patients underwent echocardiographic follow-up (median follow-up time:6 months [3, 12]). During follow-up, left ventricular out flow tract gradient was significantly decreased from (89.1±30.6) to (12.8±11.6) mmHg (P＜0.001); the number of patients with systolic anterior motion (SAM) of mitral leaflets decreased from 451(98.5%) to 42 (9.3%) (P＜0.001); 297 (64.8%) patients presented with moderate or severe mitral regurgitation before surgery, which decreased to 14 (3.1%) at follow-up (P＜0.001); the multivariate regression analysis showed that patients with residual SAM were significantly associated with a higher incidence of moderate to severe mitral regurgitation during follow-up (odds ratio 30.334, 95% confidence interval:5.619-163.739, P＜0.001). Conclusions:Extended myectomy, combined with dividing the anomalous links between mitral apparatus and septum, and trimming papillary muscles, yields satisfactory outcomes of relieving LVOT obstruction and reducing mitral regurgitation in most of patients with HOCM. Concomitant mitral valve surgery is rarely required unless the patient have intrinsic mitral valve disease.

Advance on the Biotransformation of Bioactive Natural Leading Compounds / 中国生物工程杂志

Biotransformation of bioactive natural leading compounds is a kind of bioprocess in which the structure of the added bioactive natural leading compounds could be modified by biocatalysts(e.g.,enzyme,microbial,plant and animal cells) in order to produce high efficient and low toxicity compounds.The biotransformation purpose of the known bioactive natural leading compounds is to improve its efficiency,or reduce its toxicity,or improve its solubility and bioavailability.The trace and high-valued bioactive natural leading compounds also could be produced by the biotransformation,and the biotransformation of bioactive natural leading compounds is still helpful to study the mechanism of drug metabolism.The current focus of the biotransformation of bioactive natural leading compounds is on the compounds of steroid,quinine,flavone and terpene,and some important biotransformation process has been successfully screened out.Fundamental research should be done in the following fields,such as the biotransformation mechanism of bioactive natural leading compounds,biotransformation process engineering,and the efficiency evaluation of bioproducts produced by biotransformation.The latest biotechnology(e.g.,directed evolution of biocatalyst,combinatorial biotransformation,non-aqueous biotransformation,high throughput screening) should be introduced to the biotransformation of bioactive natural leading compounds,which will boost its fast development.