Recombinant lentiviral vectors containing at least: a lentiviral backbone comprising essential lentiviral sequences for integration into a target cell genome; a nucleic acid encoding a CCR5 RNAi; and an expression control element that regulates expression of the nucleic acid encoding the CCR5 RNAi element, are provided by this invention. In an alternative aspect, the vector also contains polynucleotides encoding TRIM5 alpha and HIV TAR decoy sequences along with gene expression regulation elements such as promoters operatively linked to the polynucleotides. The vectors are combined with packaging plasmid and envelope plasmids and optionally conjugated to cell-specific targeting antibodies. Diagnostic and therapeutic methods for using the compositions are further provided herein.

Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts or tautomers thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment and/or prevention of an infectious disease (e.g., bacterial infection (e.g., Mycobacterium infection (e.g., tuberculosis)). (I) ##STR00001##

A recombinant microbial cell is capable of producing at least one compound having structural Formula II from a carbon source:

##STR00001##

In Formula II, n=2-3; R.sub.1=H or COCH.sub.3 or CH.sub.2CH.sub.2COX with X=OH or O; R.sub.2=CH.sub.3 or CH.sub.2CH.sub.2COX with X=OH or O where the cell comprises a genetic modification to increase activity relative to its wild-type cell of E.sub.4 where E.sub.4 is a desferrioxamine or bisucaberin synthetase (EC 6.3.-.-) (E.sub.4i) capable of converting N5-aminopentyl-N-(hydroxy)-succinamic acid to desferrioxamine B or H or at least one other linear desferrioxamine or bisucaberin according to Formula II.

The present disclosure provides proteolysis targeting chimeras-based scalable CID (PROTAC-CID) system that repurpose PROTACs for inducible, orthogonal, and multiplex transcriptional activation. When coupled with multi-layer genetic circuits, PROTAC-CID enables digitally inducible DNA manipulations with low basal levels. These PROTAC-CID systems can be delivered in vivo by adeno-associated virus (AAV) to allow ON-OFF genetic switches.

The present disclosure relates to heterologous production of indigoidine. Provided herein are a heterologous host cell capable of expressing a polypeptide comprising at least about 70% sequence identity to any one of SEQ ID NOs: 1-5, wherein the heterologous host cell is capable of producing indigoidine; heterologous expression systems comprising the heterologous host cell; and nucleic acids encoding the polypeptide. Also provided are methods of making indigoidine, including cell-free methods, and compositions comprising indigoidine.

The present invention relates to methods of producing compounds of interest in a recombinant microorganism. In particular, the present invention relates to using a recombinant microorganism comprising a heterologous nucleic acid encoding one or more mycosporine-like amino acid (MAA) biosynthetic enzymes (e.g., MysH) to produce compounds of interest. Compositions comprising compounds produced using such methods are also provided herein. The present disclosure also provides methods of preventing sunburn, cancer, and chronic inflammatory diseases by administering such compositions to subjects in need thereof.

The present invention provides an enzyme useful for establishing an excellent N-acyl-amino group-containing compound production system, and the like. More specifically, the present invention provides a modified enzyme comprising: (A) a modified amino acid sequence consisting of an amino acid sequence comprising mutations of one or more certain amino acid residues in an amino acid sequence of a wild type enzyme having an N-acylation activity; (B) an amino acid sequence comprising substitution, deletion, insertion, or addition of one or several additional amino acid residues in the modified amino acid sequence; or (C) an amino acid sequence comprising additional mutations of one or more amino acid residues in the modified amino acid sequence and having 90% or more identity to the modified amino acid sequence, having an N-acylation activity, and having an improved N-acylation activity to L-glutamic acid or L-aspartic acid or an improved substrate specificity to L-glutamic acid as compared with the wild type enzyme, and the like.