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Ma, Ming

Publications and source records attributed to Ma, Ming.

15 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Machine learning for geophysical characterization of brittleness: Tuscaloosa Marine Shale case study

Brittleness is one of the most important reservoir properties for unconventional reservoir exploration and production. Better knowledge about the brittleness distribution can help to optimize the hydraulic fracturing operation and lower costs. However, there are very few reliable and effective physical models to predict the spatial distribution of brittleness. We have developed a machine learning-based method to predict subsurface brittleness by using multidiscipline data sets, such as seismic attributes, rock physics, and petrophysics information, which allows us to implement the prediction without using a physical model. The method is applied on a data set from Tuscaloosa Marine Shale, and the predicted rock physics template is close to the calculated value from conventional inverted elastic parameters. Therefore, the proposed method helps determine areas of the reservoir that have optimal geomechanical properties for successful hydraulic fracturing.

Geochemistry & Geophysics↗
DOE OSTI2018

Biochemical and Structural Characterization of TtnD, a Prenylated FMN-Dependent Decarboxylase from the Tautomycetin Biosynthetic Pathway

Tautomycetin (TTN) is a polyketide natural product featuring a terminal alkene. Functional characterization of the genes within the ttn gene cluster from Streptomyces griseochromogenes established the biosynthesis of the TTN polyketide backbone, its dialkylmaleic anhydride moiety, the coupling of the two moieties to form the nascent intermediate TTN F-1, and the tailoring steps converting TTN F-1 to TTN. Here, we report biochemical and structural characterization of TtnD, a prenylated FMN (prFMN)-dependent decarboxylase belonging to the UbiD family that catalyzes the penultimate step of TTN biosynthesis. TtnD catalyzes decarboxylation of TTN D-1 to TTN I-1, utilizing prFMN as a cofactor generated by the TtnC flavin prenyltransferase; both TtnD and TtnC are encoded within the ttn biosynthetic gene cluster. TtnD exhibits substrate promiscuity but accepts only TTN D-1 congeners that feature an α,β-unsaturated acid, supporting the [3+2] cycloaddition mechanism during catalysis that requires the double bond of an α,β-unsaturated acid substrate. TtnD shares a similar overall structure with other members of the UbiD family but forms a homotetramer in solution. Each protomer is composed of three domains with the active site located between the middle and C-terminal domains; R169-E272-E277, constituting the catalytic triad, and E228, involved in Mn(II)-mediated binding of prFMN, were confirmed by site-directed mutagenesis. TtnD represents the first example of a prFMN-dependent decarboxylase involved in polyketide biosynthesis, expanding the substrate scope of the UbiD family of decarboxylases beyond simple aromatic and cinnamic acids. In conclusion, TtnD and its homologues are widespread in nature and could be exploited as biocatalysts for organic synthesis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Structural Insights into the Free-Standing Condensation Enzyme SgcC5 Catalyzing Ester-Bond Formation in the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027

C-1027 is a chromoprotein enediyne antitumor antibiotic, consisting of the CagA apoprotein and the C-1027 chromophore. The C-1027 chromophore features a ninemembered enediyne core appended with three peripheral moieties, including an (S)-3-chloro-5-hydroxy-β-tyrosine. In a convergent biosynthesis of the C-1027 chromophore, the (S)-3-chloro-5-hydroxy-β-tyrosine moiety is appended to the enediyne core by the free-standing condensation enzyme SgcC5. Unlike canonical condensation domains from the modular nonribosomal peptide synthetases that catalyze amide-bond formation, SgcC5 catalyzes ester-bond formation, as demonstrated in vitro, between SgcC2-tethered (S)-3-chloro-5-hydroxy-β-tyrosine and (R)-1-phenyl-1,2-ethanediol, a mimic of the enediyne core as an acceptor substrate. Here, we report that (i) genes encoding SgcC5 homologues are widespread among both experimentally confirmed and bioinformatically predicted enediyne biosynthetic gene clusters, forming a new clade of condensation enzymes, (ii) SgcC5 shares a similar overall structure with the canonical condensation domains but forms a homodimer in solution, the active site of which is located in a cavity rather than a tunnel typically seen in condensation domains, and (iii) the catalytic histidine of SgcC5 activates the 2-hydroxyl group, while a hydrogen-bond network in SgcC5 prefers the R-enantiomer of the acceptor substrate, accounting for the regio- and stereospecific ester-bond formation between SgcC2-tethered (S)-3-chloro-5-hydroxy-β-tyrosine and (R)-1-phenyl-1,2-ethanediol upon acid-base catalysis. These findings expand the catalytic repertoire and reveal new insights into the structure and mechanism of condensation enzymes.

Chang, Chin-Yuan↗
DOE OSTI2016

Rock2 promotes RCC proliferation by decreasing SCARA5 expression through β-catenin/TCF4 signaling

Rho-associated coiled-coil forming protein kinase 2 (Rock2), as a key effector of the small GTPase RhoA, is involved in tumor development. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of Rock2 and SCARA5 in renal cell carcinoma (RCC) remain unclear. In this study, we found that Rock2 expression was markedly increased in clinical RCC tissues compared with that in adjacent non-cancerous tissues. High expression of Rock2 was inversely correlated with patient survival in RCC, which indicated that Rock2 may be a prognostic marker in human RCC. In addition, Rock2 knockdown increased SCARA5 expression and suppressed RCC cell proliferation both in vitro and in vivo. Furthermore, we found that the β-catenin/TCF4 pathway contributed to the effect of Rock2 on SCARA5-mediated RCC proliferation. Taken together, these results suggest that this newly identified Rock2-β-catenin/TCF4-SCARA5 axis will provide novel insight into the understanding of the regulatory mechanisms of proliferation in human RCC. - Highlights: • Rock2 is overexpressed in RCC. • Rock2 may be considered a prognostic marker in human RCC. • Rock2 influences RCC proliferation by regulating SCARA5 expression. • Rock2 regulates SCARA5 expression via the β-catenin/TCF4 pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027

Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us to propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Structure of the ent -Copalyl Diphosphate Synthase PtmT2 from Streptomyces platensis CB00739, a Bacterial Type II Diterpene Synthase

Terpenoids are the largest and most structurally diverse family of natural products found in nature, yet their presence in bacteria is underappreciated. The carbon skeletons of terpenoids are generated through carbocation-dependent cyclization cascades catalyzed by terpene synthases (TSs). Type I and type II TSs initiate cyclization via diphosphate ionization and protonation, respectively, and protein structures of both types are known. Most plant diterpene synthases (DTSs) possess three alpha-helical domains (alpha beta gamma), which are thought to have arisen from the fusion of discrete, ancestral bacterial type I TSs (alpha) and type II TSs (beta gamma). Type II DTSs of bacterial origin, of which there are no structurally characterized members, are a missing piece in the structural evolution of TSs. Here, we report the first crystal structure of a type II DTS from bacteria. PtnaT2 from Streptomyces platensis CB00739 was verified as an ent-copalyl diphosphate synthase involved in the biosynthesis of platensimycin and platencin. The crystal structure of PtmT2 was solved at a resolution of 1.80 angstrom, and docking studies suggest the catalytically active conformation of geranylgeranyl diphosphate (GGPP). Site-directed mutagenesis confirmed residues involved in binding the diphosphate moiety of GGPP and identified DxxxxE as a potential Mg2+-binding motif for type II DTSs of bacterial origin. Finally, both the shape and physicochemical properties of the active sites are responsible for determining specific catalytic outcomes of TSs. The structure of PtmT2 fundamentally advances the knowledge of bacterial TSs, their mechanisms, and their role in the evolution of TSs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892

The bleomycins (BLMs), tallysomycins (TLMs), phleomycin, and zorbamycin (ZBM) are members of the BLM family of glycopeptide-derived antitumor antibiotics. The BLM-producing Streptomyces verticillus ATCC15003 and the TLM-producing Streptoalloteichus hindustanus E465-94 ATCC31158 both possess at least two self-resistance elements, an N-acetyltransferase and a binding protein. The N-acetyltransferase provides resistance by disrupting the metal-binding domain of the antibiotic that is required for activity, while the binding protein confers resistance by sequestering the metal-bound antibiotic and preventing drug activation via molecular oxygen. We recently established that the ZBM producer, Streptomyces flavoviridis ATCC21892, lacks the N-acetyltransferase resistance gene and that the ZBM-binding protein, ZbmA, is sufficient to confer resistance in the producing strain. To investigate the resistance mechanism attributed to ZbmA, we determined the crystal structures of apo and Cu(II)-ZBM-bound ZbmA at high resolutions of 1.90 and 1.65 angstrom, respectively. A comparison and contrast with other structurally characterized members of the BLM-binding protein family revealed key differences in the protein ligand binding environment that fine-tunes the ability of ZbmA to sequester metal-bound ZBM and supports drug sequestration as the primary resistance mechanism in the producing organisms of the BLM family of antitumor antibiotics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. Here, one set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Using statistical learning to close two-fluid multiphase flow equations for a simple bubbly system

Direct numerical simulations of bubbly multiphase flows are utilized to find closure terms for a simple model of the average flow, using Neural Networks (NNs). The flow considered consists of several nearly spherical bubbles rising in a periodic domain where the initial vertical velocity and the average bubble density are homogeneous in two directions but non-uniform in one of the horizontal directions. After an initial transient motion the average void fraction and vertical velocity become approximately uniform. The NN is trained on a dataset from one simulation and then used to simulate the evolution of other initial conditions. As a whole, the resulting model predicts the evolution of the various initial conditions reasonably well.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Communication: Water on hexagonal boron nitride from diffusion Monte Carlo

Despite a recent flurry of experimental and simulation studies, an accurate estimate of the interaction strength of water molecules with hexagonal boron nitride is lacking. Here, we report quantum Monte Carlo results for the adsorption of a water monomer on a periodic hexagonal boron nitride sheet, which yield a water monomer interaction energy of −84 ± 5 meV. We use the results to evaluate the performance of several widely used density functional theory (DFT) exchange correlation functionals and find that they all deviate substantially. Differences in interaction energies between different adsorption sites are however better reproduced by DFT.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

GaInN light-emitting diodes using separate epitaxial growth for the p-type region to attain polarization-inverted electron-blocking layer, reduced electron leakage, and improved hole injection

A GaInN light-emitting diode (LED) structure is analyzed that employs a separate epitaxial growth for the p-type region, i.e., the AlGaN electron-blocking layer (EBL) and p-type GaN cladding layer, followed by wafer or chip bonding. Such LED structure has a polarization-inverted EBL and allows for uncompromised epitaxial-growth optimization of the p-type region, i.e., without the need to consider degradation of the quantum-well active region during p-type region growth. Simulations show that such an LED structure reduces electron leakage, reduces the efficiency droop, improves hole injection, and has the potential to extend high efficiencies into the green spectral region.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗