tetracenomycin F2(2-)

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: tetracenomycin F2(2-)
• 英文别名: (E)-4-(3-acetyl-5,7-dihydroxy-4-oxido-10-oxo-9H-anthracen-2-yl)-3-hydroxybut-3-enoate
• 化学式: C20H14O8-2
• 分子量: 382.3
• InChiKey: OVIPDYYHLHEFDF-YIXHJXPBSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  氢(+1)阳离子 、 tetracenomycin F2(2-) 生成 水 、 tetracenomycin F1(1-)
  参考文献：
  名称：

  Structural and Functional Analysis of Tetracenomycin F2 Cyclase from Streptomyces glaucescens

  摘要：

  Tetracenomycin F2 cyclase ( tcmI gene product), catalyzes an aromatic rearrangement in the biosynthetic pathway for tetracenomycin C in Streptomyces glaucescens. The x-ray structure of this small enzyme has been determined to 1.9-Angstrom resolution together with an analysis of site-directed mutants of potential catalytic residues. The protein exhibits a dimeric betaalphabeta ferredoxin-like fold that utilizes strand swapping between subunits in its assembly. The fold is dominated by four strands of antiparallel sheet and a layer of alpha-helices, which creates a cavity that is proposed to be the active site. This type of secondary structural arrangement has been previously observed in polyketide monooxygenases and suggests an evolutionary relationship between enzymes that catalyze adjacent steps in these biosynthetic pathways. Mutational analysis of all of the obvious catalytic bases within the active site suggests that the enzyme functions to steer the chemical outcome of the cyclization rather than providing a specific catalytic group. Together, the structure and functional analysis provide insight into the structural framework necessary to perform the complex rearrangements catalyzed by this class of polyketide cyclases.

  DOI：

  10.1074/jbc.m406144200
• 作为产物：
  描述：

  氢(+1)阳离子 、 malonyl-CoA(5-) 生成 二氧化碳 、 coenzyme A 、 水 、 tetracenomycin F2(2-)
  参考文献：
  名称：

  Reconstitution of the Iterative Type II Polyketide Synthase for Tetracenomycin F2 Biosynthesis

  摘要：

  The tetracenomycin polyketide synthase (TCM PKS), a type II complex, produces TCM F2, a precursor of TCM C in Streptomyces glaucescens, and consists of at least the TcmK, -L, -M, and -N proteins. The TcmK/TcmL ketosynthase subunits were purified from overexpression of their genes in Streptomyces lividans. TcmK (calculated molecular mass 45 kd) and TcmL (calculated molecular mass 42 kd) function as a heterodimeric alpha beta complex based on observing that only the purified complex complemented TCM PKS activity in protein extracts made from strains bearing tcmK or tcmL deletion mutants to make TCM F2 in vitro, and that the molecular mass of the purified complex was 90 kd as estimated by gel filtration chromatography. The TCM PKS activity was reconstituted with purified protein components, indicating that the minimal set of proteins required to make TCM F2 included the ketosynthase complex (TcmKL), an acyl carrier protein (TcmM), a malonyl CoA:ACP acyltransferase (MAT), and a cyclase (TcmN). The MAT was required to catalyze the transacylation between malonyl-CoA and TcmM, although a relatively slow spontaneous transacylation also occurred in a reaction without the MAT. Acetyl CoA, the proposed starter unit for the TCM PKS, was not required for the production of TCM F2 in vitro, although it could be incorporated into this polyketide to a small extent. TcmJ, a PKS protein without a known function, greatly increased the production of TCM F2 but could not replace TcmN as a cyclase in the reconstituted system.

  DOI：

  10.1021/bi980466i

文献信息

• Tetracenomycin F2 cyclase: Intramolecular aldol condensation in the biosynthesis of tetracenomycin C in Streptomyces glaucescens
  作者：Ben Shen、C. Richard Hutchinson

  DOI：10.1021/bi00092a026

  日期：1993.10.1

  Tetracenomycin (Tcm) F2 cyclase, which catalyzes the cyclization of the anthrone Tcm F2 to the naphthacenone Tcm F1 in the biosynthesis of the anthracycline antibiotic Tcm C in Streptomyces glaucescens, has been purified to homogeneity and characterized. The N-terminal sequence of the enzyme establishes that it is encoded by the tcmI gene, whose deduced product has a molecular weight of 12 728. SDS-PAGE analysis gave a single band with a molecular weight of 12 500, whereas gel-filtration chromatography yielded a molecular weight of 37 500, indicating that the Tcm F2 cyclase is a homotrimer in solution. Under pH greater-than-or-equal-to 8.0, the enzyme catalyzes the cyclization of Tcm F2 to Tcm F1 and has a K(m) of 121 +/- 18.2 muM and V(max) of 704 +/- 62.3 nmol.min-1.mg-1. In contrast, under pH less-than-or-equal-to 6.5, it catalyzes the cyclization of Tcm F2 to 9-decarboxy Tcm F1, a known shunt metabolite of the Tcm C biosynthetic pathway. Tcm F2 cyclase represents the first discrete enzyme for carbon-carbon bond formation via an intramolecular aldol condensation-dehydration mechanism, a key biochemical operation proposed in the early steps of the biosynthesis of all aromatic polyketides.