Marine bacteria (n = 1,928) were isolated using Actinomycetes Isolation Agar (AIA) media and screened against bacteria causing nosocomial lower respiratory tract infections via agar overlay method. Nine Actinomycetes displayed significant antimicrobial efficacy against target pathogens, viz. Streptococcus pyogenes, Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Based on the inhibitory efficiency, SZ33 was chosen for further studies and identified as a new strain Streptomyces rochei SZ33 (OQ726229). Production of antimicrobial secondary metabolites was optimized and best results were achieved at pH 6, 20 °C, with 2% salt concentration. FTIR analysis revealed the presence of alcohol and amide carbonyl compounds. Analysis of diethyl ether extract using GC-MS confirmed the presence of antimicrobial compounds, viz. β-carotene-3,3′-diol, (3R, 3’R)-all-trans; 2H-pyran, 2-(7-heptadecynyloxy) tetrahydro; astaxanthin and aurin etc. Furthermore, docking studies demonstrated that natural compounds derived from SZ33, exhibited superior binding affinities, with larger allosteric binding pocket sites compared to conventional synthetic antibiotics.