The status of type I polyketide synthase ketoreductases

被引:33
作者
Zheng, Jianting [1 ]
Keatinge-Clay, Adrian T. [1 ]
机构
[1] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA
关键词
6-DEOXYERYTHRONOLIDE-B SYNTHASE; ERYTHROMYCIN BIOSYNTHESIS; MOLECULAR-BASIS; CELMERS RULES; FUNCTIONAL-ANALYSIS; 4-PRO-S HYDRIDE; FATTY-ACID; STEREOCHEMISTRY; DOMAINS; STEREOSPECIFICITY;
D O I
10.1039/c2md20191g
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Complex polyketides are a large group of structurally diverse and pharmaceutically important natural products known for their multiple chiral centers harboring hydroxyl and alkyl substituents. Numerous studies to decipher how stereochemistry is controlled during their biosyntheses have determined that ketoreductases usually set most of their chiral centers. While the reliable engineering of ketoreductases within modular polyketide synthases to set new stereocenters in complex polyketides has yet to be realized, this review summarizes the contributions of biochemical studies, engineering efforts, and structural biology to understanding these stereocenter-molding enzymes.
引用
收藏
页码:34 / 40
页数:7
相关论文
共 50 条
  • [21] In Vivo and In Vitro Analysis of the Hedamycin Polyketide Synthase
    Das, Abhirup
    Khosla, Chaitan
    CHEMISTRY & BIOLOGY, 2009, 16 (11): : 1197 - 1207
  • [22] Multiple Functions of the Type II Thioesterase Associated with the Phoslactomycin Polyketide Synthase
    Geyer, Kyra
    Hartmann, Steffen
    Singh, Randolph R.
    Erb, Tobias J.
    BIOCHEMISTRY, 2022, 61 (23) : 2662 - 2671
  • [23] Structural and Biochemical Analyses of Regio- and Stereospecificities Observed in a Type II Polyketide Ketoreductase
    Javidpour, Pouya
    Korman, Tyler Paz
    Shakya, Gaurav
    Tsai, Shiou-Chuan
    BIOCHEMISTRY, 2011, 50 (21) : 4638 - 4649
  • [24] Coupled Methyl Group Epimerization and Reduction by Polyketide Synthase Ketoreductase Domains. Ketoreductase-Catalyzed Equilibrium Isotope Exchange
    Garg, Ashish
    Khosla, Chaitan
    Cane, David E.
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (44) : 16324 - 16327
  • [25] Studying a Bottleneck of Multimodular Polyketide Synthase Processing: the Polyketide Structure-Dependent Performance of Ketoreductase Domains
    Schroeder, Marius
    Ross, Theresa
    Hemmerling, Franziska
    Hahn, Frank
    ACS CHEMICAL BIOLOGY, 2022, 17 (05) : 1030 - 1037
  • [26] Structural Studies of an A2-Type Modular Polyketide Synthase Ketoreductase Reveal Features Controlling α-Substituent Stereochemistry
    Zheng, Jianting
    Piasecki, Shawn K.
    Keatinge-Clay, Adrian T.
    ACS CHEMICAL BIOLOGY, 2013, 8 (09) : 1964 - 1971
  • [27] THE DEBS PARADIGM FOR TYPE I MODULAR POLYKETIDE SYNTHASES AND BEYOND
    Katz, Leonard
    COMPLEX ENZYMES IN MICROBIAL NATURAL PRODUCT BIOSYNTHESIS, PART B: POLYKETIDES, AMINOCOUMARINS AND CARBOHYDRATES, 2009, 459 : 113 - 142
  • [28] Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase
    Hong, Hui
    Sun, Yuhui
    Zhou, Yongjun
    Stephens, Emily
    Samborskyy, Markiyan
    Leadlay, Peter F.
    BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 2016, 12 : 2164 - 2172
  • [29] Biosynthesis of Akaeolide and Lorneic Acids and Annotation of Type I Polyketide Synthase Gene Clusters in the Genome of Streptomyces sp NPS554
    Zhou, Tao
    Komaki, Hisayuki
    Ichikawa, Natsuko
    Hosoyama, Akira
    Sato, Seizo
    Igarashi, Yasuhiro
    MARINE DRUGS, 2015, 13 (01) : 581 - 596
  • [30] The Determinants of Activity and Specificity in Actinorhodin Type II Polyketide Ketoreductase
    Javidpour, Pouya
    Bruegger, Joel
    Srithahan, Supawadee
    Korman, Tyler P.
    Crump, Matthew P.
    Crosby, John
    Burkart, Michael D.
    Tsai, Shiou-Chuan
    CHEMISTRY & BIOLOGY, 2013, 20 (10): : 1225 - 1234