在酵母中完成阿片类药物的生物合成
Stephanie Galanie1, Kate Thodey2, Isis J Trenchard2
1Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
概括
科学家们利用酵母来从糖中制造阿片类药物, 这种突破为种植提供了一个潜在的替代品,
科学领域:
- 生物技术
- 合成生物学
- 生物化学
背景情况:
- 在西方医学中,阿片类药物对治疗疼痛和缓解疼痛至关重要.
- 目前的阿片类药物供应完全依赖于种植, 面临气候变化和害虫的挑战.
- 确保基本阿片类药物的稳定和可持续供应是一个重大问题.
研究的目的:
- 设计用于阿片类化合物的酵母生物合成, 特别是thebaine和hydrocodone.
- 从非植物来源生产医学相关的阿片类药物的原则证明.
- 探索阿片类药物生产的替代生物技术途径.
主要方法:
- 利用酶发现和工程来识别和优化必要的催化活动.
- 设计和实施复杂的代谢途径,以在酵母中实现阿片类生物合成.
- 从多种生物体 (植物,哺乳动物,细菌,酵母) 整合酶到工程菌株中.
主要成果:
- 从简单糖中成功制造出能够生产thebaine和hydrocodone的酵母菌株.
- 实现了需要表达21 (thebaine) 和23 (hydrocodone) 酶活动的完整阿片类生物合成途径.
- 通过合成生物学方法证明了生产阿片类药物的可行性.
结论:
- 酵母可以被改造成产生关键的阿片类化合物,
- 在优化和扩展这项技术以实现商业可行性方面仍然存在重大挑战.
- 有责任的治理和公开的讨论是实现这一生物技术进步的必要条件.
相关概念视频
Biosynthesis of Polysaccharides
905
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
905
Biosynthesis in Bacteria
964
Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
964
Opioid Analgesics: Morphine and Other Natural Cogeners
1.5K
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
1.5K
Yeast Signaling
18.5K
Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
18.5K
Opioid Analgesics: Synthetic and Semisynthetic Opioids
1.5K
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
1.5K
Biosynthesis of Lipids
882
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
882


